Honr 289a the Ecology and Evolutionary Biology of Infectious Disease

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HONR 289A The Ecology and Evolutionary Biology of Infectious Disease

Fall, 2014

Art-Sociology Building (Building 146) Room 3221

Tuesday 3:30 - 6 p.m.


Dr. Benjamin Rosenthal, Adjunct Professor of Biological Sciences

brosenth@gmail.com (brosenth@umd.edu forwards to it)

301 504 5408 (office)

Office hours: by prior arrangement on Tuesdays, 2:30-3:30

Course overview:

Certain ecological and evolutionary processes are especially well exemplified by organisms that induce infectious disease and by their corresponding host responses. The advent of molecular evolutionary genetics has rendered such viral, bacterial, and parasitic organisms ideal as study subjects because microbial abundance, and their relatively rapid evolutionary potential, allows us to study (and sometimes even predict) evolutionary trajectories. That should come as welcome news, given the devastation wrought by the likes of AIDS, malaria, and avian flu.

Population genetics has been termed “the auto mechanics of evolutionary biology” because it studies how standing intra-specific variation becomes converted into distinct biological lineages. We will explore its special contribution to elucidating the biology of infection. We will also adopt the complementary perspectives of molecular evolution, phylogenetics, comparative genomics, and epidemiology. Although mastery of any of these disciplines could not be achieved through such an introductory seminar, students will gain insight into the range of questions that can be posed and tested using available tools and attainable data.

The objectives of this course are threefold:

1) To gain an appreciation for the diverse methods available to study evolutionary and ecological processes using increasingly abundant biological data.

2) To understand how these methods may be applied to real problems in infectious disease.

3) To become more critical readers of scientific literature and more precise scientific writers.

Student participation and evaluation:
Over the course of the semester, students will:
Submit six Reaction Papers (described below, and due 4pm Saturday prior to class). Your best five papers will count toward your final grade (I’ll drop the lowest-scoring paper from your tally) (up to 10pts each). (50 pts. Total)
Contribute actively to weekly seminar discussions, and serve as the student facilitator for one seminar discussion (10 pts).
Prepare a draft term paper for 2 peer reviewers (due 11/11 required but ungraded).
Provide careful and constructive reviews of two draft term papers (due 11/18, 10 pts. for completing this; reviews are not graded on a continuous scale).
Submit a final term paper (due 11/25, 25 pts).
Deliver a 12 minute presentation summarizing the term paper’s themes (on 12/2 or 12/09) (5 pts).

Reaction Papers
By semester’s end, you will be expected to submit 6 brief (~3 page) reaction papers expressing your observations, insights, and/or questions about a text or group of texts. Strong reaction papers do not merely summarize a text, but instead discuss your impressions of its content, construction, and conclusions. The strongest reaction papers integrate information and perspectives from various assigned and unassigned readings, and from class discussions.
A reaction paper documents your engagement with course materials, allowing you to specify (for yourself, for the reader) what you find important, persuasive, useful, compelling, intelligible, relevant, applicable, or worthy of further study (or what fails to do so). Write a good reaction paper and our “student facilitator” will likely seek to emphasize these ideas during class discussion. Take a position and be prepared to defend it: your favorite study may fall short in other’s eyes. Lets find out why, and learn something in the process.
How do you go the extra mile? Follow up on your questions by seeking information from additional sources. Attempt to address, as best you can, points that especially interest or confuse you. Did doing so resolve your confusion? Reinforce your hunch? Overturn your previous understanding? Take risks and tackle areas about which you feel uncertain. The best reaction papers document, briefly, a process of discovery and its results.
By devoting serious attention to your reaction papers, you will:

1- learn about the subject at hand

2- gain experience wrestling with (sometimes challenging) texts

3- improve your skill at succinctly expressing your observations and opinions

4- prepare yourself for classroom discussion
A thoughtful reaction paper may well develop the ideas you seek to explore in greater depth through your term paper.
Reaction papers are due, via e-mail, to the instructor and to the student facilitator by 4pm on the Saturday prior to class.

Course evaluation
I encourage you to take the opportunity to evaluate this course. This feedback helps me make teaching improvements and helps future students make informed choices. Your participation is rewarded by allowing you to see how other courses have been evaluated.
CourseEvalUM will be open for students to complete their evaluations in early December at www.courseevalum.umd.edu.

Students who complete evaluations for all of their courses in the previous semester (excluding summer), can access the posted results via Testudo's CourseEvalUM Reporting link for any course on campus that has at least a 70% response rate.

Academic support

If you are experiencing difficulties in keeping up with the academic demands of this (or any other) course, contact the Learning Assistance Service, 2202 Shoemaker Building, 301-314-7693.  http://www.counseling.umd.edu/LAS Their educational counselors can help with time management, reading, math learning skills, note-taking and exam preparation skills.  All their services are free to UMD students.Course schedule:

Week 1- September 2
Assignments for this week-

Read over the syllabus. Think about what caught your eye about this course, and why you chose to attend.

Classroom agenda:
Introduction to the content and conduct of this course.

A. Questions.

Why should evolutionary biologists and ecologists pay attention to infectious disease?
Are such diseases still important?
What potential might evolutionary and ecological perspectives contribute to understanding, preventing, or ameliorating infectious diseases?
What characteristics of infectious diseases are inherently evolutionary or ecological?
B. A taste of what’s to come:

A brief overview of the course content- themes and problems we’ll emphasize.

C. Introductions. Do you have specific interests? How might this course fit into your overall educational goals?
D. Overview what successful student participation entails in a seminar.
E. Preview course assignments and opportunities for participation.
F. Overview structures in scientific writing that promote clarity, even when certain terminology or methods may be unfamiliar. We will pay attention to how papers are presented, with the hope that our own contributions will emulate the best of these.
G. Overview proper attribution in scientific (indeed in all academic) writing: Generously and accurately acknowledge whose observations and interpretations lay the foundation for your own understanding of things.

Week 2- September 9
Assignments for this week-

1. Biology, Evolution, and Infectious Disease: Convergence and Synthesis

Bruce R. Levin, Marc Lipsitch, Sebastian Bonhoeffer


2. Population dynamics of flaviviruses revealed by molecular phylogenies. Paolo M. De A. Zanotto, Ernest A. Gould, George F. Gauo, Paul H. Harvey, and Edward C. Holmes. Proc. Natl. Acad. Sci USA Vol. 93 pp 548-553, Jan 1996.
3. Use Google Scholar (scholar.google.com) or the ISI Web of Knowledge “trace the roots” or “follow the trail” of any of these three articles.

(To sign in to the ISI Web of Knowledge, you’ll need to type in the 14-digit number that appears above the barcode on the back of your University ID). http://www.webofknowledge.com.proxy-um.researchport.umd.edu/?DestApp=WOS

4. This is your first opportunity to write a reaction paper. Incorporate what you learned from both the original paper and one of its antecedents or successors. It will be interesting to discuss the diverse directions this takes the class.
5. Optional: Find an hour to listen to this. http://www.onbeing.org/program/meaning-intelligence/208

It has nothing to do with infectious disease, but quite a bit to do with teaching and learning, and therefore deserves some consideration as we embark. Best would be to download to an ipod/phone and go for a walk or a run. Wherever you listen, allow yourself to slow down, log off of Facebook, and just be attentive for an hour. It's admittedly, even intentionally, slow.

6. *On October 29th, we'll discuss Alfred Crosby’s Ecological Imperialism: The Biological Expansion of Europe, 900-1900. Now would be the time to order yourself a copy, or find it in the library. (Either edition will do).

Week 3- September 16
Assignments for this week:
1. Read something about the basic biology and transmission of three of the following diseases: Malaria, Toxoplasmosis, AIDS, Tuberculosis, Avian Influenza, Cholera, Human papillomavirus.
Books, review articles, research papers, websites provide such information and serve as portals to additional resources. (Note: the quality of any information source must be assessed, and this is especially so for information on the web, which may or may not have undergone critical peer review. For this particular assignment, cdc.gov provides a good starting point; I am aware of, but do not personally subscribe, to the view that Wikipedia inherently lacks scholarly credibility. I think that's often a fine place to start, and encourage you to apply the same scrutiny to it as to any source: how well substantiated are this entry's claims? How rich are its sources? Do its conclusions mirror ones I find elsewhere? If you use it, treat it as a point of entry rather than a final destination).

2. The July 26th, 2012 issue of Nature http://www.nature.com/nature/journal/v487/n7408/index.html contained at least four papers related to the Ecology and Evolutionary Biology of Infectious Disease:

One elucidates how malnutrition makes people susceptible to intestinal disease (thereby exacerbating their malnutrition, and contributing tragically to the toll that famine can take).
Another describes a drug that forces latent HIV 'out of hiding', which may open new avenues to combatting the recurrence of symptoms, reducing the infection risk that individuals harboring subclinical viral loads continue to pose to others, or even curing someone of HIV infection.
One examines the common, and unique immunological cascades provoked by various types of viral infection.
The last seeks to better understand how various viral proteins disrupt the processes that otherwise constrain the growth of human cells, characterize in general terms the networks thereby perturbed, and then use such insights to more clearly understand cancer formation when no such viruses are present.
(If that isn't exciting enough, you can read the next article that heralds a new age in combatting baldness!)
Your mission: familiarize yourself as best as is reasonably possible, given about 20 minutes of effort for each paper, with its general aims, approaches, and findings. Then choose one of these upon which to focus special attention. This one you should really work at, as though your comprehension of its nuances mattered (not so much in the sense that you'd be quizzed on it, but more in the sense that your assessment of it would influence a clinical decision, would influence this team’s opportunity to receive additional research funding, or would influence a newspaper's decision to report on such discoveries). About the other three, prepare yourself only to the extent that you could engage in a conversation about the basics, or ask some educated questions of those more familiar with the study.
If you are writing a reaction paper this week, focus on the paper that you opted to 'adopt.' Weigh in on A) how effectively you believe the principal aims, observations, and conclusions have been explained and B) any ideas it brings to mind that you think merit follow up. You need not understand every technicality embodied within the paper. Make your best effort to grasp the most important aspects of the findings and conclusions being advanced, understanding that you have not necessarily been exposed to all the background that would be necessary to comprehensively assess its merits.
Classroom agenda:

A. Round robin on the biology and epidemiology of several important diseases.

Who read about Malaria, and what did you learn? How is it transmitted? Where? To whom? Under what circumstances?
Who read ab out Toxoplasmosis, and what did you learn?

Who read about AIDS, and what did you learn?

Who read about Tuberculosis, and what did you learn?

Who read about Avian Influenza, and what did you learn?

Who read about Cholera, and what did you learn?

Who read about Human papillomavirus, and what did you learn?

Which of the articles in Nature did you choose to focus on, and why?
What did you learn? What left you perplexed? Did you get something out of the articles that struck you as less interesting or accessible? What strategies did you use to overcome any barriers that you encountered in seeking to understand and evaluate such articles?

Week 4- September 23
Assignments for this week:

1. Chimpanzee Reservoirs of Pandemic and Nonpandemic HIV-1

2. Limitations of a Molecular Clock Applied to Considerations of the Origin of HIV-1
3. The Geographic Spread of the CCR5 delta HIV-Resistance Allele.
4. A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1


Classroom agenda:

AIDS, the zoonoses. Understanding the origins of HIV and modeling the determinants to its management or spread.

The evolutionary genetics of resistance to HIV

Week 5- September 30
Assignments for this week.
1. Malaria’s Eve: Evidence of a recent population bottleneck throughout the world populations of Plasmodium falciparum

by Rich et al.

2. Recent Origin of Plasmodium falciparum from a Single Progenitor by Volkman et al.

3. Haplotype Diversity and Linkage disequilibrium at Human G6PD: Recent Origins of Alleles that confer malarial resistance.

4. Origin of the human malaria parasite Plasmodium falciparum in gorillas

Classroom agenda:

Malaria’s Eve:

Evidence from parasite population genetics

The age of human adaptations to malaria

Week 6- October 7

Assignment for this week:

1. Read an introduction about antigentic shift and antigenic drift in influenza viruses at: http://www.cdc.gov/flu/about/fluviruses.htm#how
2. Predicting the evolution of Influenza A.
3. Ecological and immunological determinants of influenza evolution.

4. Structural and genetic basis for development of broadly neutralizing influenza antibodies

5. Find a press account about ongoing efforts to monitor Avian Influenza in domestic poultry, wild birds, or people.

Classroom agenda:
Influenza- viral reassortment, antigenic drift, and successive strain replacement.
Influenza genomics and future risk.
Week 7- October 14
Assignments for this week:
1. Read the Wikipedia page providing an overview of Mathematical modeling in epidemiology:


You will not be quizzed on the math here. But make an effort to see where they are trying to go with this. Play with some scenarios and see if the relationships make sense to you.
2. Read and come ready to discuss “Antiretroviral Drugs for Tuberculosis Control in the Age of HIV/AIDS” by Williams and Dye, a paper that uses such a perspective to forecast the effects of particular health policies.
3. Read and come ready to discuss “Limited good and limited vision: multidrug-resistant Tuberculosis and global health policy” by Kim et al.
Classroom agenda:
Basic epidemiological models- and its relationship to ecology more generally.
Ecology of pathogen interaction: TB and HIV.

Transmission parameters and the political forces that shape them: cost-effectiveness in TB control.

How should these tools be applied to understanding Ebola?!

Week 8- October 21
Assignments for this week:
1. Read enough of “How clonal are bacteria?” of John Maynard Smith et al so that you think you understand what is being conveyed by figure 1. Don’t feel compelled to review all of the data in the paper. Save time for the following three papers on Toxoplasma gondii (which is not bacterial).
2. Success and Virulence in Toxoplasma as the Result of Sexual Recombination Between

Two Distinct Ancestries Grigg et al.

3. Globalization and the population structure of Toxoplasma gondii by Lehmann et al.

4. Recent expansion of Toxoplasma gondii through enhanced oral transmission by Su et al.

Clonality- a concept borrowed from bacteriology.

Grigg et al and the clonal model for Toxoplasma gondii.
Is it more complicated than that?

Lehmann et al.

Week 9- October 28
Assignments for this week:
1. Read Ecological Imperialism: The Biological Expansion of Europe by Alfred W. Crosby.

*Yes, this is 300 pages. Please plan accordingly.

2. Read Evolution, consequences and future of plant and animal domestication by Jared Diamond
Nature 418, 700-707 (8 August 2002)


3. Do any diseases currently rival those described above in their social impact? Are there any you fear may? Find something to read that discusses an ongoing or anticipated scourge, and relate it to what you have read about past pandemics.
Classroom agenda:
Discuss Ecological Imperialism and its perspective on past pandemics.
Continue discussion…and its relevancy to ongoing and feared future epidemics.

Week 10- November 4
Assignments for this week:
1. Readings:

Population structure and the evolution of virulence in nematode parasites of fig wasps

Crossing the line: Selection and Evolution of Virulence Traits

Convergence of the secretory pathways for cholera toxin and the filamentous phage ctx

Experimental evolution of Parasites
Classroom agenda:

The Evolution of virulence: evidence from ‘natural experiments’

The evolution of virulence: evidence from controlled experiments.

Week 11- November 11
Assignments for this week:

  1. Readings:

HIV-1 Evolution and Disease Progression

Var genes

Deceptive imprinting

2. Complete your draft term paper.

Prepare your draft term paper for peer review. Submit it to me electronically by the beginning of class, November 11.

NUMBER the lines of your text to ease the reviewer’s need to direct comments and suggestions to specific portions of your text. In Microsoft Word, this can be accomplished as follows:

  1. On the File menu, click Page Setup, and then click the Layout tab.

  2. In the Apply to box, click Whole document.

  3. Click Line Numbers.

  4. Select the Add line numbering check box, and then select the options you want.

I will send your paper to two peer reviewers.

See the next week to understand what your reviewer will be looking for.

Classroom agenda:
Variable surface antigens: moving targets

Immunodominant antigens: deceptive targets?

Week 12- November 18
Assignments for this week:
1. Go to the Library. I'm not kidding. Actually go. Find one of these books in the stacks. Don't hesitate to ask a librarian for help should you need assistance locating it. If the book it catches your interest, pull it off the shelf and read its introduction, its table of contents. If it looks interesting, snap a photo of yourself with it at the shelf where it resided, check the book out, and read at least one additional chapter. What? Someone already checked it out? Well, you can search out your second best option; but before you go, have a look around the books in that section. If you find something else that grabs you, select it (and snap that picture).
Bring your book in so you can introduce it to us, and tell us why we ought (or ought not) read it. (when's the last time you had show-and-tell in class?!)
You may write a reaction paper about what you learned from the book or books that you found, how the content expands upon what you've been learning in class; while doing so, you may also reflect on the experience of acquiring information….."old school". What was limiting or frustrating about searching out information bound in physical volumes? Were there any unexpected benefits? Will you likely go back? (be honest)
Plagues and peoples

William H. McNeill.

Anchor Press, 1976.
Guns, germs, and steel : the fates of human societies

Jared Diamond. W.W. Norton, c1997.

Principles of population genetics

Daniel L. Hartl, Andrew G. Clark.

Sinauer Associates, c1997.
An illustrated guide to theoretical Ecology

Ted J. Case. Oxford University Press, 2000.

Molecular evolution : a phylogenetic approach

Roderic D.M. Page and Edward C. Holmes. Blackwell Science, 1998.

Infectious diseases of humans : dynamics and control

Roy M. Anderson and Robert M. May. Oxford University Press, 1991.

Evolution of infectious disease

Paul W. Ewald. Oxford University Press, 1994.

Immunology and evolution of infectious disease

Steven A. Frank. Princeton University Press, c2002.

Essentials of human parasitology

Judith S. Heelan, Frances W. Ingersoll. Delmar, c2002.

Evolutionary genetics : from molecules to morphology

edited by R.S. Singh and C.B. Krimbas. Cambridge University Press, 2000.

Fundamentals of molecular evolution

Dan Graur, Wen-Hsiung Li. Sinauer Associates, c2000.

New uses for new phylogenies

edited by Paul H. Harvey Oxford University Press, 1996.

The origin of AIDS

Jaques Pepin. Cambridge University Press. 2011.

2. Perform a thorough review of each of the two projects you have been provided.

Your review should address both the concepts underlying the paper, as well as the mechanics of its execution.
Are the issues to be discussed clearly delineated?
What are the most interesting issues being raised in the paper?

Can you state the central objective or theme of the paper? Has the author done so in a concise and interesting way?

Do these objectives seem achievable within the scope of such a paper? You may suggest other vantage points to broaden the paper or, perhaps, recommend those areas deserving most emphasis if the study seems overly diffuse.
Is sufficient background information provided in the introduction, and is it thoroughly referenced?

Is subsequent information presented in a logical order?

What parts are written with greatest clarity? Are there rough spots that seem vague, awkwardly worded, or repetitive?

Does each paragraph develop a particular idea or point?

Do any issues merit further attention or clarification?

Do any inaccuracies require correction?

Are points of conjecture qualified as such?

Is the writing precise? Does it define specialized terms? Are grammatical or spelling errors evident?

Do its conclusions seem justified?

Was it a satisfying what did you learn?

Having read the paper, do you believe the title succinctly conveys the essence of the matter? (You may suggest alternatives).

DOES THE PAPER GENEROUSLY AND ACCURATELY ACKNOWLEDGE whose observations and interpretations lay the foundation for each idea? DRAFTS LACKING literature citations throughout the text and a bibliography will be returned (after instructor approval) without comment (ouch! Please do not make this mistake).

Reviewers should point out any places where he or she cannot easily discern the provenance of an idea or phrase, or where the text could reasonably be interpreted as claiming for its author credit for ideas or language rightfully attributed to others. In other words, does the text consistently explain who helped develop the ideas and observations that support (or refute) ideas discussed in the paper?
Is the reference section, itself, complete and consistent?
Be fair….and as constructive as possible. Remember that there are diverse ways of effectively presenting ideas (not all conforming to your own preferences). Provide the author concrete feedback for strengthening their work. The author will be looking to you for advice they can actually USE in the remaining time- reviews recommending that the entire idea be scrapped are not likely to be viewed with sympathy!
Remember- peer review’s purpose is to help safeguard the quality and integrity of published work (such review determines whether and where a given paper will be published). Publishers and editors depend on this process to ensure that the content of their text is sound.
Authors, themselves, are also protected in the process…because the need to satisfy knowledgeable and careful reviewers improves the writing upon which an author’s reputation will be based. As a reviewer in our course, you are providing an essential service to the author by offering constructive advice.
Week 13- November 25
1. Complete your term paper. Give serious consideration to your reviewer’s suggestions for strengthening its content and/or organization. Please bring a hard copy to class on November 25 and also e-mail me copy no later than 12pm that day.
2. Readings

Disparate rates of Molecular Evolution in Gophers and their chewing lice

Myth of Eve
Elucidating other facets of evolutionary biology using the variability of pathogens and their hosts.
Co-phylogeny and relative evolutionary rates
Does the number of ancestral alleles tell us something about the number of ancestors we’ve had?
Course evaluations may be completed at www.courseevalum.umd.edu beginning December 3rd. Please do this for the benefit of future students. I won’t see these until well after the semester ends, after grades are in, and after this will all be a memory to you. But the response rate needs to be high (especially in a class this small) in order for me, for the University, and for future students to assess the course’s value, strengths, and weaknesses. So please visit the site and share your feedback.

Week 14- December 2 Student Presentations (1)
Assignment for this week:

Prepare an oral presentation of your final project (10-12-minutes, plus 3 minutes for questions; generally 4-5 slides does it). Outline your interests, what you set about to learn, what you found, what you concluded, and perhaps what you see as interesting future work. PRACTICE your talk in front of a willing friend to see how long it really takes, what came off clearly, and what you need to better explain or illustrate. Practice it again (preferably on a new “victim”) to see how well you’ve smoothed the rough edges. It might seem awkward to ask for 15 minutes of someone else’s time, but such practice will build your confidence and help you accurately assess your presentation’s length.

If you will be using Powerpoint (or Apple's Keynote, or Prezi…..) please send me your slides by 9:00 am Monday December 2nd. That will give me time to get them organized on a single drive, saving us class time. It will also preclude your endlessly fussing over the slides; a strong talk requires being organized about what you want to say (and recognizes the limits of what can be said) in a short period. Neither goal is served by reworking slides till the moment of presentation (a conclusion many practicing scientists have yet to learn!).

Week 15- December 9

Classroom agenda:

Student Presentations (2)

Wrap Up, Course conclusion.

Reminder: Please evaluate the course at www.courseevalum.umd.edu.
I won't know whether or not you've done so, and doing so has no influence on your grade (faculty aren't appraised of student feedback until long after the conclusion of the semester). But your evaluation will help me understand the strengths and weaknesses of the class, and will help future students decide what they ought to consider taking.
• Academic Accommodations:  If you have a documented disability, you should contact Disability Support Services 0126 Shoemaker Hall.  Each semester students with documented disabilities should apply to DSS for accommodation request forms which you can provide to your professors as proof of your eligibility for accommodations.  The rules for eligibility and the types of accommodations a student may request can be reviewed on the DSS web site at http://www.counseling.umd.edu/DSS/receiving_serv.html.

• Religious Observances:  The University System of Maryland policy provides that students should not be penalized because of observances of their religious beliefs, students shall be given an opportunity, whenever feasible, to make up within a reasonable time any academic assignment that is missed due to individual participation in religious observances.  It is the responsibility of the student to inform the instructor of any intended absences for religious observances in advance.  Notice should be provided as soon as possible but no later than the end of the schedule adjustment period.  Faculty should further remind students that prior notification is especially important in connection with final exams, since failure to reschedule a final exam before the conclusion of the final examination period may result in loss of credits during the semester.  The problem is especially likely to arise when final exams are scheduled on Saturdays.

• Academic integrity: The University of Maryland has a nationally recognized

Code of Academic Integrity, administered by the Student Honor Council. This Code sets standards for academic integrity at Maryland for all undergraduate and graduate students. As a student you are responsible for upholding these standards for this course. It is very important for you to be aware of the consequences of cheating, fabrication, facilitation, and plagiarism. For more information on the Code of Academic Integrity or the Student Honor Council, please visit http://www.studenthonorcouncil.umd.edu/whatis.html

The University of Maryland is one of a small number of universities with a student-administered Honors Code and an Honors Pledge, available on the web at http://www.jpo.umd.edu/aca/honorpledge.html.  The code prohibits students from cheating on exams, plagiarizing papers, submitting the same paper for credit in two courses without authorization, buying papers, submitting fraudulent documents, and forging signatures.  The University Senate encourages instructors to ask students to write the following signed statement on each examination or assignment:  "I pledge on my honor that I have not given or received any unauthorized assistance on this examination (or assignment).”

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