The same virus that turned the rabbit into a Jackalope.

The papillomavirus which causes warts on the skin is usually defeated by the immune system in approximately one year. You can have your warts removed, but until the virus is defeated by the immune system, warts will continue to recur. In 2000, in Indonesia a man named DeDe was dubbed the Tree Man, when doctors removed over 13 pounds of warts from his body. Unfortunately, due to his compromised immune system, the warts recurred. When the papillomavirus presents internally in humans, just like with rabbits, it can cause cancer to grow. Pharmaceutical companies developed a vaccine for HPV, which targets the two most prevalent strains (which account for nearly 70% of cervical cancer cases), but we are each host to hundreds of different strains of HPV and they are constantly acquiring new mutations and swapping DNA or genes. If vaccines decimate the 2 most prevalent strains, do you think natural selection may favor the evolution of any of those other strainsafter all we cant underestimate something that using only eight genes can make whole villages afraid of rabbits.

Distribute textbooks (The Hot Zone)

While distributing books, allow students to re-design their procedures given the new information presented in the mini-lecture. As you approve their procedures, let them begin implementing their experiments (review lab safety, etc.)

Week 1, Day 3: Pick your Poison

Scientists estimate that there are 10000000000000000000000000000000 viruses. Thats like more than 10 million times more viruses than there are stars in the universe! If you were to stack one virus on top of another, youd create a tower that would stretch beyond the moon, beyond the sun and beyond the edge of the Milky Way! You need to write a one-page summary of each. Okay, just kidding. But if we each study one virus that affects humans and give a 3 minute presentation on how it replicates and how humans combat it, well each know about 60 of those 1031 viruses, and thats a pretty good start! Heres your challenge: Deliver a 3-minute lecture that tells us about your virus brief history, how it attacks, replicates and mutates and also any efforts to eradicate it. This isnt a history of HPV (for example), its more about letting us learn how HPV has survived for centuries, from a cellular to more abstract level. I would encourage you not to use notecards. There may be a prize for not using notecardswe will determine that next week. Before you present next Friday, youll need to practice for two different classmates (during class time). 1

I would like you to give written feedback to the two practice rounds that you watch. Here is one possible format for providing what is hopefully helpful feedback to your peers. My Name: My presentation was within 20 seconds of 3 minutes It clearly explained how the virus replicates It clearly explained how the virus has evolved and/or is evolving It explained whats been/being done to try to eradicate it I avoided ums, uhs, pauses, I spoke clearly and was loud enough I didnt use notes, made eye contact Please give me 2 positives and 2 suggested improvements. Thank you!! Peer-reviewer #1: Peer-reviewer #2:

Please feel free to use another templateI will check in with you as youre practicing. Ill also ask you to turn in the feedback forms when you present to the class. If the feedback was clearly internalized (made evident through your presentation), the entire class will earn an extra plate of E. coli. Youll also need to submit two review questions which help us focus on the most important points of your presentation. Train your weaknesses. Race your strengths.

Are viruses dead or alive? Are they parasites?

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Popcorn read Something in the Forest & guided discussion

Elephants in Kitum Cave, mining for salt1 Based on our discussion on Monday of the virus findings in the Sierra de Naica caves, what do you think was in Kitum Cave? Lets talk about the use of fire. How do you think intentional burning effects biodiversity and/or the movement of microbes? Why wont antibiotics work on viruses? How many people do you think Monet came into contact with between the time he began showing symptoms and the time of his death? How do you think Monet contracted the virus which killed him? How many possible sources of infection could there be in the cave?

Week 1, Day 4
Students work on eradicating Severe Acute Respiratory Syndrome (SARS)
We will explore the website (http://www.odec.ca/projects/2005/ wang5d0/public_ html/MainPage. htm) of an eleventh-grade student (named David Wangcoincidence?) who designed an affordable, efficient, orally-administered plant-based vaccine for SARS through experimentation and his knowledge of genetics. Not the goalbut one idea of the many possibilities that are there for you! Abstract of project: The SARS-coronavirus (SARS-CoV) is the viral pathogen causing severe acute respiratory syndrome (SARS). There are no vaccines available yet that can protect against the virus. Several lines of evidence suggest that the virus establishes its infection via mucosal routes. Production of oral vaccines to induce specific mucosal antibody response will therefore represent the most effective approach to preventing SARS infection. In this study, a synthetic gene encoding an antigenic region of the SARS-CoV Spike protein that induces neutralizing antibodies was fused with a bacterial gene coding for cholera toxin B subunit (CTB), a mucosal carrier molecule for the efficient generation of mucosal antibody responses to linked antigens. The CTB-Spike (CTB-S) chimeric gene was under the control of the double CaMV 35S promoter.Agrobacterium-mediated transformation was used to introduce the chimeric gene into tobacco plants. PCR analysis confirmed the presence of the CTBS genes in the transgenic plants. The expression of the CTB-S gene in the transgenic plants was demonstrated by northern blot hybridization and western blot analysis. GM1 binding ELISA assay showed that the CTB-S fusion protein efficiently binds to the mucosal GM1 receptor. The availability of transgenic plants expressing CTB-S provides a solid foundation for the development of a plantbased, safe, cost-effective, edible vaccine against SARS.2 While visiting and exploring the website, review the format of a scientific experiment and scientific
1 2

Preston, Richard via Dr. Ian Redman. http://richardpreston.net/guide/hz/download.html

Wang, David. 2005 Science Project. http://www.odec.ca/projects/2005/wang5d0/public_html/Abstract.htm

report: How to choose a hypothesis3? Experimental process What did I do in a nutshell? What is the problem? How did I solve the problem? What did I find out? What does it mean? Who helped me out? Whose work did I refer to? Extra Information
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Section of Paper Abstract Introduction Materials and Methods Results Discussion Acknowledgments (optional) Literature Cited Appendices (optional)

In pairs, students brainstorm ideas for their hypotheses and any questions they would ask of the expert scientists

Skype Chat with Scientists

Allow Dr. Wang or one of his colleagues to explain in full the study they conducted and the results. Allow students to follow up with any unanswered questions about the prior study, nematode behavior, how to design an experiment, etc.

Design Partner Plans for Project What do you want to test?

The remainder of the class will be spent finalizing the research project in pairs and beginning first implementation steps (writing out procedures). Check in on the infected worms, award prize if 75% or more of class worms are showing atypical intestinal structures when viewed under microscope. Tomorrow, class will receive a new pair of healthy worms to mate. At that point they should have an F 1 healthy generation and an F1 infected generation. Depending on the unique experimental design of each pair, partners may try to mate worms first or infect them first.

Week 1, Day 5:
Bates College, Department of Biology. 2002. How to Write a Paper in Scientific Journal Style and Format. http://abacus.bates.edu/~ganderso/biology/resources/writing/HTWsections.html
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Cartoon. 2007. http://immobilienblasen.blogspot.com/2008_01_01_archive.html 4

Mini-Challenge #2: What do you make of this diagram?

This will be on the board throughout the day

Viral Replication in a closed population: Challenge: Figure out who is the original carrier of the virus! Given: You each have a cup filled with equal amounts of clear liquid. Required: You each need to interact with at least three people (by pouring half of your liquid into their cup, and then they do the same). Sequence: After each person has interacted with three others, I will give you a new, helpful item. You have 15 minutes to figure out who originally had the virus; if you are correct you will earn 5 filtratesand can decide how to distribute them later. Go! *Hint: Devise a plan as a class before you begin mixing* In advance teacher will: Fill cups to equal level (less than half full I think will reduce the amount of clean up) Fill all but one cup with water and one with sodium hydroxide If needed, answer questions, but try to let students do it on their own After the interactions, give them Phenolphthalein (PPT will do acid/base reaction and turn pink if in the presence of NaOH3) Facilitate discussion on process and implicationshow could a virus spread in our school? How quickly could it happen (relate to The Hot Zone) Class vote on what the schematic represents

Mating Lab
After the viral replication lab in which the students are representing gene shuffling and viral DNA 5

and RNA mixing, we will show the process of mating the worms on the overhead projector. It is slightly tricky to do, so the teacher should demonstrate how to do it. If time remains in the period, allow the students to attempt to mate their own nematodes. If not, teacher will have to do it after the class period ends. I found this resource most helpful in learning about C. elegans: Worm Breeding for Dummies. http://worms.zoology.wisc.edu/pdfs/WBD.pdf

Week 2, Day 2: Mini-Challenge #3: Immune System Simulation

Do Now: Brainstorm several action verbs you associate with the cell or role in the left column. For example, if the thing was cell wall, I might brainstorm verbs like: guards, separates, holds, protects, or others and write them in the second column Now you go! You have 5 minutes! Thing or Role Virus/Pathogen Memory B-Cell Helper T-Cell Antibody Macrophage Antigen Body Cell Pair-share for third column (words or phrases that could finish the S-V clause) For example, for Memory B-Cell, individuals may have brainstormed remembers or recognizes and in pairs they might say recognizes a virus/pathogen, remembers a previous infection or attack To make this more real, lets use a metaphor of a hat factory, where a normal happy cell makes good, pleasant hats, but a rogue, sinister virus (with a super ugly hat) tries to take over the factory. What might each of these roles be in that metaphor? (May find it easier to work together as a class) Action Word or Phrase Association Metaphor

AAACHOO! Oh no! Ms. Durkee, Four Rivers co-founder is sick! We have reason to believe she may have the rhinovirus. As we all now know, there is no cure for the common cold, and Ms. Durkee doesnt want us to make her any chicken noodle soup or ginger ale. Instead, shes asked us to show her whats going on in her body at the molecular level. You need to figure out a way to model the immune system, so that when she comes by the class to visit in fifteen minutes, shell be able to clearly understand how her immune system is fighting the virus. Oh, and since cells cant talk, you wont be able to explain your demonstration with words. Materials for you: Spiky hats Smooth hats Construction paper Tape Markers, Pens, Pencils Ask if you feel you need others If Ms. Durkee can explain your demo to us all correctly, everyone gets one actively infected, mature C. elegans! Allow students to re-vise and redo if she has questions or confusion; dont tell them this initially. Assessment and Discussion What role did you play? How did the interaction work? Could it have gone on forever? What if youd had twice as many (choose the cell type they had less of, virus/pathogen, T-cells, etc.)? Exit Activity: Write three quiz questions for Ms. Durkee based on the activity and what you helped her to learn about viral infection and the immune response. These will be used later in the week during the relay based challengeno need to explain that now

Week 2, Day 3:
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Influenza Vaccine Lab (stats cited from CDC, WHO, in text)

Why do we get the flu more than once? Are vaccines ineffective? How sloppy are viruses? When they replicate, genes get shuffled often, causing rapid mutations that result in the creation of new viral strains constantly. The CDC estimates that viruses evolve one million times faster than human genes. As viruses change, even slightly, the memory B-cells in your immune system (created by prior exposure to the virus or through introduction by vaccination) no longer recognize or remember the virus. Unlike your brain, which would identify that these two are actually the same

Your immune system wouldnt recognize that, and would have to fight Doc Oc, even if had just gotten rid of Otto Octavius or been vaccinated against Otto. Which is why the CDC has to develop a new flu vaccine every year! Once your immune system defeats Doc Oc, will its work be complete? Does this relate to natural selection and evolution? Powerpoint Lecture & Discussion. Does the immune system facilitate the evolution of increasingly deadly viruses? Do vaccines? The viral strains which dont evolve (change their proteins) are ousted by the immune system and are progressively less able to replicate and are eventually wiped out. Those that do evolve, force the immune system to do work, which takes time (isnt it easier to defeat a known adversary than one youve never played against beforewhy do you think Bill Belicheck was always secretly filming other teams practices?). In the time it takes your immune system to fight back, you become sick and as a host to the virus, you pass it along through your sneezing, sniveling, coughing and snotty-nose wiping, to name a few. 8

Human antibody formed from a previous exposure to a viral strain (antigen) matches a particular coat protein (the antigen). This kind of match spurs the immune system into immediate action that prevents the virus from causing re-infection. Relate to both prior exposure and vaccination. (highly simplified)

Contrast with that antibody encountering a slightly mutated viral antigen (notice how still very similar imagine if very different). Does not recognizemeaning the surface of its coat is not a compatible locking or shutdown mechanism. Time it takes for immune system to develop a fitting antibody is determined by overall health and the challenge posed by the new viral antigen (HIGHLY SIMPLIFIED!). Why can you catch the flu multiple times in one season? In addition to this constant evolutionary cat and mouse game in which the virus mutations stay one step ahead of your immune system, several strains of influenza virus survive and reproduce in other animal hosts. For that reason, even if all humans in a given area acquire resistance to the virus, those strains can survive in other species long enough to mutate and infect humans again later on. Case Study: Avian Bird Flu (this will be an example of the 3-minute lecture that students present later in the week) Challenge! Working in new pairs, design an influenza vaccine based on (a simplified version of) current viral toxicity data from the CDC. Hint CardHow are Vaccines made?
Every year, nearly 30 million doses of flu vaccine are rolled out that force the immune system to create antibodies to three different flu strains. How do scientists decide on the top three out of millions of choices? Very carefully; after looking at a lot of data. On what data are those predictions based? The CDC constantly receives virus samples from all over the world. Each sample is logged into a database that records where it came from, the degree of illness it caused and whether it infected only a few

isolated people or seemed to be spreading rapidly. Each strain is genetically fingerprinted and compared with known strains. Parts of the original samples are kept on ice, and parts are incubated in chicken eggs or special cultures to be grown for further study. Samples whose proteins surfaces look different enough to pose a serious threat are further tested see how infectious they are and how long it takes the immune system to respond to them. Throughout the entire process, the cultured strains are monitored to make certain that they haven't mutated too much from the original samples. In the meantime, researchers in the lab stay in constant contact with public health officials and fieldworkers in the parts of the world where the most "interesting" strains originated. Why? Because, for reasons that still arent understood, some strains spread quickly in human populations, while others just don't get around very much. The results of all these studies are combined, analyzed and presented to expert panels at a meeting of the FDAs Vaccines Advisory Committee. Then the debates begin. Which strains produce the most serious symptoms? Which spread from person to person most effectively? Which strains seem to be emerging from the areas in which they first appeared? Which are staying put? Which of the potentially serious strains can be grown well enough in the lab to produce enough vaccine? Finally, a decision is made about which three strains are most likely to cause the most trouble in the United States the following winter. You did WHAT to my baby?!? Once the decision is made, the rush to manufacture the vaccine takes off! The chosen viral strains are inoculated into 90 million fertilized chicken eggs in which the viruses incubate. The eggs are opened, and the virus is extracted and purified. Then the virus is treated chemically to kill it while preserving the normal shape of its coat proteins. Each final dose of vaccine is very small, containing scarcely fifteen millionths of a gram of each of three different viral strains. Yet that tiny amount of foreign protein, injected into your body, is enough to place your entire immune system on red alert. Assuming that you are vaccinated at least a week before you are exposed to live virus, your B-cells and T-cells will be ready to defend you but only against the three strains contained in the vaccine.

So roll up your sleeves, and lets make vaccines!

Week 2, Day 5: Relay-based challenge activity

Using the questions the class generated during the immune system simulation and those submitted with their case study presentations, determine if any key elements are not touched on and add questions that challenge remaining misconceptions during the intervening week. Divide the class into five teams of four students each, and prepare the classroom to have as much open space as possible (or if you can use the gymwith power outlets that would be even better). I have prepared a quizlet (online website sort of like Prezi) as a model, but you would likely make your own based on the students unique questions. Here is a sample link: http://quizlet.com/4011809/spacerace/ that is a game. The one I created is also available there. 10

Each team member races to the laptop at the end of the room and attempts to answer a question. If they answer correctly, the quizlet gives them a green light, and they race back to their team, slap hands and let the next person continue the quiz. If they answer incorrectly, they must race back to their team and discuss the question and what the team thinks is the best answer, then return and try to solve. All teams have the same questions, but quizlet shuffles the order, so not all teams will be answering the same question at the same time. Each member of the team that finishes first wins one Orsay filtrate which they can share with their lab partner or gift to another pair. The results of each teams answers are instantly uploaded to the quizlet designers profile, so the teacher can see which questions were most commonly missed, etc. Final ten minutes will be spent reviewing the most missed questions.

Week 3, Day 2:

Take a Stand on Vaccines

Two vaccines are used throughout the world to prevent polio. One, developed by Jonas Salk, is similar to the influenza vaccine we studied last week, in that it is comprised of three wild, virulent and inactivated strains of polio virus and administered in an intramuscular injection. The second, is a live-attenuated vaccine, incubated in chimpanzee tissue and administered orally. Between 1957 and 1960, over one million Africans (living in present-day Kinshasa, DRC, Rwanda and Burundi) were given this oral polio vaccine (OPV) in a massive (and usually forced) experimental trial vaccine campaign. OPV is preferable as it is easier to administer, cheaper and less painful than an IM injection. To incubate and amplify the vaccine, the kidney cells of local chimpanzees and green monkeys were harvested. The oldest confirmed sample of human tissue that shows the presence of HIV is an archival sample of plasma collected from an anonymous donor in the city of present-day Kinshasa in 1959, leading researchers to believe that it entered into the population shortly before 1959. Based on what we know of viruses and vaccines, it is possible that HIV, which is most closely related to SIV (Simian Immunodeficiency Virus) of chimpanzees and green monkeys jumped species through these trials. Remember, this remains a highly debated controversy, and no one is certain how HIV came about. Do you think it is okay to test vaccines on people when were not sure of the effects of testing that vaccine? If most of the class stands closer to the end of the L-shaped continuum disagreeing, try to find out why they disagree. Is it wrong because the people tested upon were not consenting? o What if an even greater number of people died because of not developing a vaccine? 11

Is it wrong because we could be creating a much more virulent strain? o Wouldnt natural selection balance out the host-pathogen co-evolution in time? o Is it right for scientists to intervene in nature? Is it wrong because we do not know the potential outcome (segue into Precautionary Principle)? o Discuss instances where both action and inaction have been detrimental (DDT, Thalidomide, allergies, etc.)

Week 3, Day 4: How is HIV different than other viruses? Sketch artist challenge:
Challenge: Individually, choose to create a comic strip a Wanted Ad or some other visual representation demonstrating the mechanism by which HIV attacks the human immune system, and how your immune system responds!
Categories Organization and Preparation Class Participation A Project which Meets Expectations: Your project is neat, complete and wellorganized. It is submitted at the end of the period. You are on-task and hard at work on your project. You do not require reminders to stay at work. You ask for help if you need clarification or have questions about the project. Your project includes specific details that accurately explain how HIV is transmitted, how it replicates and how the immune system seeks to combat it, including the
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Science Concepts

Science Communication

incorporation of first lines of defense, white blood cells. An exceedingexpectations project would also include the correct use of memory B-cells and helper T-cells. The book is visually pleasing and creative. It has clear hand-written or typed text as well as illustrations or pictures. The illustrations do not have to be hand drawn.

Hot Zone Discussion Groups and Focus Questions

Short Answer Summative Assessment for The Hot Zone:
1. Describe and/or diagram three possible reservoirs for the virus. 2. What makes Kitum Cave such a great place for a virus to jump species?

Richard Preston at the mouth of Kitum Cave

3. Why do you think Peter Jahrling wanted a sample of Dr. Ian Redmans blood? What do you think he thought we might find in it? 4. Describe Tom Geisberts experiment about dormancy of the Marburg virus. What were the results? How does this compare to HIV? 5. Why are spiders continued to be suspect in the hunt for the original host of Ebola? What about the sharp-rock hypothesis? List as many possible hosts as you can remember from the various theories of the scientists in the book. 6. What does the author have to say about HIV's path to the outside world as a consequence of habitat destruction? Explain and justify your agreement or disagreement with the authors sentiments. 7. What makes a really effective virus? Describe and/or diagram in finite detail.

Assessment Rubric for Meeting Expectations

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Final Scientific Report Section Abstract (10 points) Expectations

Is a short, concise paragraph which states how you accomplished your objectives Makes brief mention of methods, results and conclusions Demonstrates relevance to field or suggests contributions to future study Clearly states objectives and outlines plan for implementing Engaging to the reader Summarizes the science concepts guiding the investigation Provides background on the study by Dr. Wang and his colleagues, and how your investigation relates to existing knowledge Clearly states the problem, hypothesis and the data measured by experiment and investigation Detailed yet concise description of the materials used and procedures followed, including any changes to methodology at the mid-point of the research Includes all data tables, calculations and figures needed to support your findings Does not draw conclusions or make interpretations Thorough and specific interpretation of results Explains how this adds new knowledge to the fieldor how it refutes results of current work Draws final conclusions and summarizes research

Teacher Feedback

Introduction (10 points)

Literature Review (15 points) Hypothesis (problem statement 5 points) Methods and Materials (15 points) Results (15 points)

Discussion & Conclusion (30 points)

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