Handbook for Teachers

Curriculum for TranslatingTranslation and

Scientific Questioning

Engaging Students in Translational Biomedical Science and Research

This Handbook is not to be reproduced or disseminated without permission of Marlys H. Witte,MD, Professor of Surgery, Director, Student Research Programs, University of Arizona Collegeof Medicine. March, 2014

This project is supported by NIH OD R25OD010487–Translating Translation and ScientificQuestioning in the Global K-12 Community, NIH NIAID R25AI097448–Infection andImmunity K-12 Science Program: Exploring Knowns/Unknowns via VCRC/Q, NIH NHLBI1R25 HL108837–Short-Term Training to Increase the Diversity Pipeline in Heart/Lung/Blood Research, NIH NINDS R25NS076437–High School Student NeuroResearch Program (HSNRP),and NIH NICHD R25HD080811–Summers in Children’s Research for Diverse High SchoolStudents. All rights reserved. Its contents are solely the responsibility of the authors and do notnecessarily represent the official views of NIH, OD, NIAID, NHLBI, NINDS, or NICHD. Allcontents ©2014 Arizona Board of Regents.

Contents

Project Overview .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

The Curriculum: Translating Translation and Scientific Questioning (TT/SQ).. . . . . . . . 3

The Questioning Theme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

What’s This All About? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

The Wonder of Ignorance � Curiosity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

The Ignorance Map . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Attention and Perception. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Fact or Fiction: Scientific Truth.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Asking Questions Can Challenge Assumptions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Questioning and the Scientific Process = Fun and Surprises.. . . . . . . . . . . . . . . . . . . . . 13

Are There Answers and Does It Matter?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

What Makes a Question “Good” or Interesting?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Exercises in Questioning. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Student Project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Student Reflections on Questioning.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

The Translational Theme. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Translational Science and the Research Enterprise. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

What is Translational Research?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Examples of Translational Research (Penicillin, DNA, Vitamin B12). . . . . . . . . . . . . . 24

Science Is a Social Activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

The Research Enterprise. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

How External Factors Can Affect Translation.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Student Project Resources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Exercises in Translation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Student Reflections on Translation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Overview of Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

TT/SQ Curriculum: Putting it all together - with your signature . . . . . . . . . . . . . . . . . . . . 38

Epilogue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

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Project Overview

e have been inspired to develop thisTranslating Translation and ScientificQuestioning program and curriculum as

a way to share with you and your students theexcitement, learning adventure, andextraordinary success of a workshop seriesdeveloped at the University of Arizona byProfessor of Surgery Dr. Marlys Witte and hercolleagues. The seven-week workshop, whichis offered every summer, has the startling title,“Summer Institute on Medical Ignorance”(SIMI); and it consistently emboldensstudents to ask questions that express theirinherent curiosity and can lead to meaningfulresearch.

This unique program champions ignorance – the kind that leads to authentic, originalquestions. The kind that Nobel physicistDavid Gross called, “our most importantresource” and “the most important product ofknowledge.” The kind that Nobel physicistRichard Feynman said he felt a responsibilityto “as a scientist who knows the great value ofa satisfactory philosophy of ignorance, and theprogress made possible by such a philosophy,progress which is the fruit of freedom ofthought.” This is the kind of ignorance thatignites fresh, imaginative thinking and is thespringboard to discovery.

We hope that this curriculum will inspire andexcite you, and will nourish our upcomingyoung thinkers by nurturing and sustainingtheir innate curiosity, their questioning minds,and their ignorance. Once you have seen whatwe mean by extolling the virtues of thisseemingly very negative word and havereviewed this guide to incorporating aphilosophy of ignorance into the sciencecurriculum you teach, we hope you will honorand reward your students for their willingnessto embrace ignorance by asking questions,rather than repeating or producing answers.What they ask might not only lead to newknowledge and insights we cannot yetimagine – they might also lead to unimaginedsolutions when translated and applied toreal-world issues such as in medicine.

Our overarching goal is to promote studentcuriosity, motivation, skills, networking, andcareer pathways in science, particularly toreinvigorate the clinical research enterprise.But the importance of recognizing and dealingwith ignorance applies to all authentic inquiry.Long-term outcomes document that ourface-to-face “ignorance-based” scienceeducation approach and teacher trainingcomponents reinforce the “joy” of learning,creativity, and sense of adventure sparked byquestioning the unknown.

Ignorance is the kind of not knowing that comes from insight and leads to insight. That insight -the one it comes from and the one it leads to - is the discovery that there is a world far largerthan the one that is known, one that (whether we know it or not) shapes all our knowns. It is aworld we know nothing about, though if we search we can catch glimpses of it. Ignorance is thenot knowing that opens us up to philosophical wonder, to scientific discovery, to human wisdom.

– Gerald Nosich, PhDProfessor of Philosophy, University of Buffalo

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The Curriculum: Translating TranslationAnd Scientific Questioning

ost science classes focus on thescientific method: formulating tractable

research topics, developing experiments totest those hypotheses, and making inferencesbased on the outcomes of those experiments.But our program and its companionweb-based platform-grid the Virtual ClinicalResearch Center and Questionarium(VCRC/Q) focuses on two complementarytopics or themes: Where we find goodquestions to pose for research purposes, and –once we have completed a round of basicresearch – how we translate the knowledgeand insights we have gained into end-pointsthat address real-world issues and solutionsthat make a difference in the lives of others.

Our experience has shown how crucial it isfor students to understand that the bestquestions come from their intrinsic curiosityabout the world and to realize that basicresearch which remains trapped in thelaboratory may end up as little more than aself-satisfying exercise for the investigator.We therefore focus on encouraging studentsto love science and to want to engage inpro-social outcomes of their scientificexplorations. Teaching this philosophy ofresearch and these skills form the basis of thetwo-part curriculum we present here: theTranslating Translation and ScientificQuestioning Curriculum (TT/SQ)

To facilitate your students’ learning process,this site and the VCRC/Q website will serveas dynamic and evolving repositories ofbiomedical research. Currently, this site mapsthe status of the Translating Translation andScientific Questioning curriculum; and it willserve, upon its final launch, as an introductory

outline for teachers. We invite you to check inregularly to view its progress and thenbecome a contributor together with yourstudents.

Throughout the curriculum, we provide andrely upon the following supportive materialsand resources, which are sometimes presentedin a variety of sequences to match theteaching needs of each segment:

Teacher Information – Background readingor foundational material that supports the keyconcepts of the section and provides a contextfor the exercises and projects that follow.Some of the teacher resources we provide –especially videos – might be interesting andthought-provoking for your students. Weencourage you to share them at yourdiscretion, and have already included a few inthe resources for classroom exercises anddiscussion. We also encourage you to sharewith your students any of the quotes aboutscience that you think would inspire orinterest them. And encourage them tocontribute their own.

Narrative – A written outline of thecurriculum that we give our students at theUniversity of Arizona. It is not a script to beread to them – it simply conveys some of ourthoughts about the ideas we cover and theybecome immersed in during our seminars andtheir research experience.

Class Exercises – Designed to help studentsfeel confident about asking questions in frontof their peers, who tend to equate questioningwith not being smart. The focus of thecurriculum always remains on Albert

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Einstein’s learning philosophy: “Theimportant thing is not to stop questioning.” Tofacilitate this kind of learning, exercisesinclude handouts that have been refined overthe years by the Summer Institute on MedicalIgnorance conducted at the University ofArizona.

| Video Resources – Segments of videos tospark student engagement and discussion. Weand our students have created many videosduring past seminars and workshops, andthese samples are available to you and yourstudents. We have also been given permissionby TED Conferences, LLC, to incorporaterelevant segments of video presentations fromTED Talks. Finally, the curriculum teachesstudents to produce their own videos as a finalproject – one of many forms such a projectcan take. Our experience supports the ideathat one of the best ways to learn a topic is toconstruct a final project that teaches others;and allowing students a choice of formats,from a video presentation to poster sessions,gives them freedom of choice.

Web Links – While the web provides a hugerepository of data that can become usefulinformation when individuals apply it, not allsources of information on the web meritconsideration. So part of the curriculumaddresses web literacy. Other links will takeyour students to interesting, fun sites thatcomplement and reinforce key concepts of thecurriculum, such as Crash Course videos onYouTube (if you find those sites appropriate).The goal of this project is to make the entirecurriculum available within a web-basedenvironment, so that students anywhere canappreciate why questioning is the key toscientific progress, and become excited by theopportunity to ask what they wonder about.

The material below describes the underlyingcurriculum that will be made available. Whenit is ready for public beta testing, the online

version will also be available here at theMedical Ignorance website. In addition,relevant state standards will be posted andupdated as needed.

The Questioning Theme

Since the heart of this project is ourconviction that students must becomeintrigued by science in order to engage in it, itis essential for us to stimulate and foster theircuriosity. Over the years, our primaryinvestigators and staff have demonstrated thatteaching students to ask questions about theirworlds piques their interest and leads tobetter, more tractable research questions.The Questioning Curriculum presents anoutline of suggested activities for you andyour students. Teachers with a wide variety ofteaching styles and the need to comply withlocal course requirements consistently comeaway from our seminars at the University ofArizona convinced of, and committed to, thebasic idea that science only advances throughasking questions, and that questioning skillscan be refined in the classroom.

What’s This All About?

Although most teachers appreciate thatstudents must be curious if they are to becomeengaged in science, encouraging scientificcuriosity is not generally a mainstay ofcurricula in middle or high schools. Teachersare faced with so many demands to cover thematerial required for standardized tests thatthey cannot individualize the curriculumaccording to each student’s interests. Butrecent standards implementations emphasizethe roles of inquiry and questioning. Thiscurriculum is therefore designed to provideyou with some ways to incorporate thesevalued skills into existing science curricula.

Our goal is to create a learning environmentthat is safe for questioning and incorporates

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the curriculum and technology students havegrown up with, including social media,computers, and mobile devices. But we wantto emphasize that the fundamental principlesof this curriculum can be shared in anyclassroom, with or without technology.

Teacher Information

1. Video on the role of technology in engagingstudents in scientific inquiry. – 2:21 minuteshttp://www.adobe-creativity.com/HED/ 2. Background information on encouragingstudents to formulate questions. http://hepg.org/hel/article/507#home

3. Video by Sir Ken Robinson: How to escapeeducation’s Death Valley (and the irony of “NoChild Left Behind”) – 19:11 minutes http://video.ted.com/talk/podcast/2013S/None/SirKenRobinson_2013S-480p.mp4

4. “Creativity And Why It Matters” – publishedby Adobe Systems – 22-slide PowerPointA study of professionals presents stunningfindings on their views of creativity. http://wwwimages.adobe.com/www.adobe.com/content/dam/Adobe/en/education/pdfs/adobe-creativity-education-findings.pdf?trackingid=KEVTN

Curiosity is the engine of achievement. - Sir Ken Robinson

Narrative

Every time I hear of a new invention or a newcure, I wonder, “What led up to that? How inthe world did they discover that?” Forinstance, how could someone ever figure outthat giving people small doses of the poliovirus could actually help eradicate polio?

Most inventions and discoveries begin withbasic questions. Curiosity, imagination, andconfusion all lead to questions that we could

pursue the answers to. And the questions areoften quite simple - they are why, how, when,and where questions.

As I hope you’ll see, asking questions is thevery first step in scientific research anddiscovery. And we’ll be spending more timethan most science classes talking aboutquestions, including what kinds make forgood research.

When Richard Feynman, the Nobel Laureatequoted in the Overview, was a graduatestudent at Princeton, he was so curious aboutother fields that he asked to sit in on some oftheir classes. Before his first class in biologymet, the guys who had invited him to take thecourse wanted to show him some things undera microscope. As Feynman describes it:

They had some plant cells in there, and youcould see some little green spots calledchloroplasts (they make sugar when lightshines on them) circulating around. I lookedat them and then looked up: 'How do theycirculate? What pushes them around?' Iasked. Nobody knew. …it was not understood at thattime. So right away I found out somethingabout biology: it was very easy to find aquestion that was very interesting, and thatnobody knew the answer to. – From Surely You're Joking, Mr. Feynman; 58

Unfortunately, some people are intimidated byscience. They think it’s difficult. If youhappen to be one of those people, rememberthat the natural world we live in is the mostawesome mystery there is. So just think ofyourself as a detective (or as an explorer, ifyou prefer) who notices things in your dailylife that puzzle you or grab your attention.You are on the lookout for evidence of somemystery – or some new territory – and youwant to explore and understand it. It’s a greatway to approach science and have fun with

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this class. And the less you take for grantedwhat you see in the natural world around youor accept without question what anybody elsehas told you, the more interesting yourquestions are likely to be. When you watchthe video coming up, think of how simpleFeynman’s question is about the ball and thewagon. Just step back and really look at whatyou see - and really see what you look at.

Class Exercises

How would you define the word “question”?

If you had to explain to a non-native Englishspeaker what question means, and you were prettysure they didn’t have a word that directlytranslated the idea, how would you explain it?Really think about it.

Possible definitions:

1. “A sentence worded or expressed so as toelicit information.”(http://en.wikipedia.org/wiki/Question)

2. “Something that is asked.” – from Webster’sdictionary

| Video Resources

1. Can a focus on questioning really make adifference? Ideas come from asking questions.Adam Savage tells a good story about RichardFeynman asking why a ball rolled to the back of awagon when he began to pull it. 7:32 minutes;suggested excerpt: 0:00 - 1:24 minutes Excerpt http://www.ted.com/talks/how_simple_ideas_lead_to_scientific_discoveries.html

2. Video by Sir Ken Robinson: How to escapeeducation’s Death Valley (and the irony of “NoChild Left Behind”) – 19:11 minuteshttp://video.ted.com/talk/podcast/2013S/None/SirKenRobinson_2013S-480p.mp4

3. “Creativity And Why It Matters” – published

by Adobe Systems – 22-slide PowerPointA study of professionals presents stunningfindings on their views of creativity.http://www.images.adobe.com/www.adobe.com/content/dam/Adobe/en/education/pdfs/adobe-creativity-education-findings.pdf?trackingid=KEVTN

The Wonder of Ignorance �Curiosity

The quote below expresses beautifully whatwe mean when we applaud ignorance, andwhat we hope to help restore to the scienceclassroom through this curriculum.

Ignorance is excitement, the perpetualchallenge to grow. Ignorance is everythingyet to be: places you've yet to go; peopleyou've yet to meet; facts you've yet to learn;things you've yet to discover. Ignorance isviewing the world through the eyes of a childfor whom all is fresh, new and unexpected.Ignorance is the possibility of surprise.

– Robert Root-Bernstein, PhDProfessor of PhysiologyMichigan State UniversityMac Arthur Foundation "genius"

Teacher Information

1. Medical Ignorance website at the Universityof Arizona.http://www.medicalignorance.org/

2. Stuart Firestein Ignorance website atColumbia University.http://ignorance.biology.columbia.edu/firestein/

3. A compilation of brief answers from 150people, from all walks of life, about what makesthem curious.http://curiosity.discovery.com/question/what-makes-you-curious

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Figure 1.

Narrative

“Ignorance” can have very negativeconnotations, like stupid or dumb. But that’snot what I mean when I use the word. In fact,inspired by her NYU medical school mentor,physician-essayist Lewis Thomas, Dr. MarlysWitte has spent the last 30 years teachingmedical ignorance and celebrating itsimportance in advancing science. Dr. Witte isa Professor of Surgery at the University ofArizona’s College of Medicine, and isDirector of its Medical (and other) StudentResearch Programs. She has gained aninternational reputation as an expert inlymphology (lymph, lymphatics, lymphocytes,and lymph nodes in health and disease) and,with her husband surgeon Charles Witte, hasauthored more than 400 peer-reviewedpublications. An international educator, shehas been dubbed the “ignoramamama” –founder of the Curriculum on Medical (andother) Ignorance – a global multidisciplinarymovement to recognize and deal with “whatwe know we don’t know, don’t know we don’t

know, and think we know but don’t.” As shesays, “ignorance – i.e., unanswered questionsand unquestioned answers – is the rawmaterial of knowledge, and (current)knowledge id the raw material of (future)ignorance, i.e., answers and questions shiftwith time and the accumulation of answers.”Simply stated, ignorance is the domain of allwe have yet to learn and discover.

None of us has the answers to all or evenmost questions in any domain of science – andjust think of the infinite number that have yetto be asked. We’re very ignorant about lots ofthings, and the more you embrace ignorance,engage in curiosity, and enjoy the questionsyou ask, the more fun you’re going to havewith science. And the more knowledgeableyou will become because as 17th centurymathematician Blaise Pascal envisioned,“Knowledge is like a sphere – as it enlargesso too does its contact with the unknown”(Figure 1) – that is, the more you know, themore you recognize that you do not know!

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Reference: Witte, M, P Crown, M Bernas, FGarcia: “Ignoramics” in medical andpremedical education. J Inv Med 56: 897-901.This article reviews the evolving concept ofignorance in general and in medicine and itsrelationship to knowledge. Goals, content, andassessment of such ignorance-based coursesare discussed. Ignoramics and questioning is away to balance the information-overloadedscience/medical curriculum.

| Video Resources

1. A compilation of brief answers from 150people, from all walks of life, about what makesthem curious.http://curiosity.discovery.com/question/what-makes-you-curious 2. Dr. Marlys Witte talks about her experienceswhen she decided to teach a course on medicalignorance. 18:04 minutes; several relevantexcerpts Sample Excerpthttp://www.youtube.com/watch?v=u3SGNvMcNdI

Class Exercise

How would you define the word “ignorance”?

Before discussing the topic, ask, “What comes tomind when I say someone is ignorant?

What are the connotations? Why do you think ithas those associations?”

Think of examples where you ignorance helpedyou - and where it harmed you.

Discuss the different dimensions of ignorance.

How does the "information gap" relate tocuriosity? The Ignorance Map

Hand out our map of the domains in the land of

ignorance (Figure 2 ) and stimulate a brainstormdiscussion of the types of questions that wouldfall into each category of the map in general or ina specific discipline of study.

The Ignorance Map

Attention and Perception

Observation is often identified as the first stepof the scientific method. But criminal trialsand our own experiences have taught us thatnot everyone observes the same thing whenthey look at the same scene. In fact, it is notuncommon for any number of people whowitness the same event to see it differently.Why is that? Nobody knows all of thereasons, which range from psychological tophysiological. But a simple way to think aboutit is that different things interest differentpeople, and those are the things that draw ourattention. Some examples of differences inperception are provided in the readings andvideos below.

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Teacher Information

1. The role of visual perception in attention – from the Scientific American.http://www.scientificamerican.com/article.cfm?id=the-role-of-visual-attent

2. An autistic man whose perceptions arewoven together to produce a very differentunderstanding of the world. A good example ofjust how really different people’s perception canbe. – 10:54 minutes http://www.ted.com/talks/daniel_tammet_different_ways_of_knowing.html

3. “Parallels between Perception withoutAttention and Perception without Awareness” – ascholarly article.http://www.arts.uwaterloo.ca/~pmerikle/papers/Merikle.ConsCogn.1997.pdf

4. “A Boolean Map Theory of Visual Attention”– from the Learning Perception and Attention Labhttp://www.pashler.com/Articles/Huang_Pashler_PR2007.pdf 5. Attention arises through a host of complexprocesses that contribute to consciousness itself. – 55 PowerPoint slideshttp://www.csun.edu/~vcoao0el/de361/de361s104_folder/sld002.htm 6. Movie perception test video by the makers ofthe Invisible Guerilla – 2:10 minuteshttp://www.youtube.com/watch?v=6JONMYxaZ_s

Narrative

Nobody knows all of the reasons whyeveryone sees things differently. Reasonsrange from the psychological to thephysiological. But a simple way to think aboutit is that different things interest differentpeople, and those are the things that draw ourattention. Some examples of differences inperception are provided in the reading andvideos below.

Where do you think questions come from? It

may seem like we’re over-analyzing a verysimple concept. But let’s think about it. Whatif we didn’t have all the senses we have? Whatif some of our senses are not as keen as thoseof our friends? We all have differentbackgrounds and assumptions that have comeabout because of how we grew up. Ourparents might have taught us much of whatwe assume to be true about the natural world.Do you think all parents explain the world inthe same ways? We are also influenced byfriends. If a good friend of yours tells yousomeone else is a jerk, won’t you beinfluenced by that?

Then what happens if you hear or experiencethings that don’t match the assumptionsyou’ve made? Ever wonder why someone elsefeels cold when you feel warm? Get surprisedwhen you find out something works totallydifferently from what you were told?

One thing that creates questions in our mindsis trying to explain surprises in the worldaround us. What we perceive, what we hear,smell, taste, and feel. And we are even morelikely to have questions when what weperceive contradicts expectations about ourworld - when something goes against whatwe’ve learned or seems odd because it’sdifferent from what we assume. What interestsme might not interest you. But what’s funabout good science research is that, withinreasonable constraints, you get to askquestions about things that interest you orstrike you as odd. And I’m going to encourageyou to question, question, question, until youfind an interest you want to pursue.

So let’s step back. What I’m saying is thatobservation - using all your senses - is alwaysthe first step in coming up with questions thatwill interest you. And since we want you to beinterested in something that is important toyou, we need to talk a bit about attention,perception, and observation.

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First, you have to bring to your attention whatyou notice – you have to notice that you’renoticing. Focus on it and become fully awarethat you are paying attention to this thing.The more open-minded you can be andapproach it with wonder instead of anyjudgment you’ve been told to make about it,the more open your mind and eyes will be toseeing it in new ways, and the fresher yourperspective will be.

Class Exercise

Have the entire class observe something together,and ask them to jot down everything they notice.What they observe could be as simple (andcomplex) as a flower or a kitchen tool. Ask themto try to look at it like they’ve never seen it before(maybe they haven’t). What strikes them about it?What do they think the different parts of it arefor? Does anything surprise them or seemmysterious? Is there anything they feel they don’tunderstand about it? Of all the things theyobserve, what interests them most, and why?What question(s) do they have about it?

Allow ample time for them to share theirresponses to observing “the same” thing and letthem discuss the similarities and differences, aswell as any questions they have. Focus on havingeach student share what interested them most, andexplain why. Then follow up with the videoresources.

| Video Resources

1. Gavin Pretor-Pinney: Cloudy with a chance ofjoy talks about overlooking the commonplace.10:54 minutes (many excerpts or entirepresentation) http://www.ted.com/talks/gavin_pretor_pinney_cloudy_with_a_chance_of_joy.html

2. Illusions that make us question our ability tosee objectively. 14:36 minutes (many excerptscould be used)http://www.ted.com/talks/al_seckel_says_our_brains_are_mis_wired.html

3. Video about perspective, produced by thePhysical Science Study Committee. In manyways, the introduction to theories of specialrelativity is demonstrated in this 1960 film. 13:21minutes (many excerpts could be used)http://www.youtube.com/watch?v=pyBNImQkRuk

4. Pass-the-basketball selective attention test. Afine example of how we tend to see what we wantto see or are told to focus on-and how, because ofthat, we might miss other things. – 1:22 minutes.http://www.youtube.com/watch?v=vJG698U2Mvo

5. Movie perception test video - Did you reallysee what you saw? – 2:10 minutes.http://www.youtube.com/watch?v=6JONMYxaZ_s

Fact Or Fiction: Scientific Truth

Scientific knowledge is constantly in flux, soit can be misleading to claim that there arescientific facts. It might be more constructiveto think of scientific knowledge as our bestunderstanding, to date, of the naturalphenomena we know about.

The discoveries of quantum mechanicsprovide an excellent example of this. WhileEinstein’s theory of relativity was generallyaccepted as fact by the scientific community,the astonishing and seemingly bizarre findingsand questions that have emerged fromquantum mechanics – about how sub-atomicparticles behave – call into question thephysical laws that had been the veryfoundation of physics. What was thought tobe known and predictable, based on the truthof those laws, has been so deeply shaken thatEinstein spent his last years trying to find away to reconcile the contradictions.

Teacher Information

1. Video on the half-life of facts. – 12:01minutes http://www.youtube.com/watch?v=GaxYnvd7YAM

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2. Change in knowledge is inevitable becausenew observations might challenge prevailingtheories.http://www.project2061.org/publications/sfaa/online/chap1.htm

3. Paleontologist Jack Horner describesastonishing new findings about dinosaurs thatdrastically shift our understanding. Great story. –18:23 minuteshttp://www.ted.com/talks/jack_horner_shape_shifting_dinosaurs.html

Narrative

Appreciating the fact that we can be easilyconfused about the world around us willprobably increase the number of questionsyou have about your world, science, andnature. And your questions are likely to bedifferent from my questions, because differentthings interest each of us, as we discussed.But if you’re willing to ask questions,including questions that you used to thinkwere dumb, you might become the next greatscientist - simply by looking for answers toyour own unique questions. That’s why youmight have heard some teachers say, “Thereare no dumb questions.” That’s not just apolite way of encouraging you to feel betterabout yourself - it’s the truth. As I mentionedbefore, who would have ever thought it wouldbe smart to ask, “I wonder what wouldhappen if we injected the polio virus intopeople?”

I know that many of you feel like it’s difficultto ask questions, especially in class.Somebody might think you’re dumb, or youmight be shy and don’t want to draw attentionto yourself. But science is only possible ifeach of us questions the world around us,including things we think we know, thingspeople won’t tell us, and things that seemimpossible to know.

Even if you aren’t interested in becoming ascientist, learning to ask questions is not onlyfun and interesting – it can also help you toget jobs in related fields that you might wantto explore. For example, if you ask questionsabout epidemics or medical breakthroughsthat occur, or you learn about the processthat the medicines in Walgreens wentthrough, it can help you in unexpected waysin the future.

So here’s another excerpt of a talk by Dr.Beau Lotto, a neuroscientist, where heencourages you to question your acceptednotions, and illustrates how the quality andenjoyment of science will increase.

| Video Resources

The class discussion that follows is based onthe presentation below, in which Lotto thinksall people (kids included) should participate inscience and, through the process of discovery,change perceptions. It also illustrates theexhilaration that comes from exploring theunknown. 16:31 minutes; many excerptscould be used. http://tinyurl.com/d5wvg2z

Class Discussion

What do you think of Dr. Lotto’s assertion thatgood science is brought about by askingquestions, often about things we think we alreadyunderstand? What do you think of the idea thatplay is similar to conducting scientific inquiry?Does that work for you? Does the analogy falldown anywhere? Would you add additional pointsto Dr. Lotto’s list below, or qualify it somehow?

o Celebrate uncertaintyo Adaptable to changeo Open to possibilityo Cooperative o Intrinsically motivated

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Asking Questions Can ChallengeAssumptions

Asking questions that surprise people,because the answers seem so obvious to them,can lead to a contradiction of theirexpectations, good and bad. When youquestion what people believe in, surprisingthings can happen.

Teacher Information

1. Challenging assumptions in education. –From Natural Life Magazinehttp://www.naturallifemagazine.com/0006/assumptions.htm

2. How the opposite of our assumptions mightalso be true. – 2.42 minuteshttp://www.ted.com/talks/derek_sivers_weird_or_just_different.html

3. An economist re-examines the statistics onAIDS in Africa and concludes that everything weknow about the spread of HIV on the continent iswrong. – 15:38 minuteshttp://www.ted.com/talks/emily_oster_flips_our_thinking_on_aids_in_africa.html

4. Thinking Critically – Community Toolbox – The University of Kansashttp://ctb.ku.edu/en/tablecontents/sub_section_main_1120.aspx

5. Paleontologist Jack Horner describesastonishing new findings about dinosaurs thatdrastically shift our understanding. Great story. –18:23 minuteshttp://www.ted.com/talks/jack_horner_shape_shifting_dinosaurs.html

Narrative

When you ask questions, especially ones thatpeople think they know the answers to, theymight get annoyed. Asking questions like thatcan challenge people’s expectations, both in

relation to social behavior and their ownworlds. You might be asking questions thatforce them to re-examine the obvious, at leastwhat seems obvious to them – or you might beasking them to consider something they don’tlike. Scientists such as Galileo, whosupported Copernicus’s view that the earthwas not the center of the universe, paid a dearprice for challenging the accepted thinking ofhis time. And when Lewis Thomas wrote“Fear of Pheromones” in 1974, heacknowledged that it might make peopleuncomfortable to think that human beingsproduce weird chemical signals similar tothose that insects use:

What are we going to do if it turns out that we[humans] have pheromones [chemicalsubstances secreted externally to conveyinformation to others and produce specificresponses on their part]? What on earthwould we do with such things? With therichness of speech, and all our new devicesfor communication, why would we want torelease odors into the air to conveyinformation about anything? …Why a gas, ordroplets of moisture made to be deposited onfence posts? – Lewis Thomas, The Lives of a Cell

But re-examining the obvious can be fun.Look what happens when a researcher inworld health re-examines the assumptions ofsome of his students.

| Video Resources

1. When Hans Rosling spoke at the US StateDepartment in the summer of 2013, he used hisfascinating data-bubble software to burst mythsabout the developing world, and reinforced theneed to continue to question “facts.”http://www.ted.com/talks/hans_rosling_at_state.html Excerpt: 0:00 - 2:50 minutes

2. Paleontologist Jack Horner describesastonishing new findings about dinosaurs that

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drastically shift our understanding. Great story. –18:23 minuteshttp://www.ted.com/talks/jack_horner_shape_shifting_dinosaurs.html

Class Discussion

One of the most important parts of any projectyou will be doing in this class is to learn to ask areal question that interests you. We will talk aboutthe scientific method, which aims to help yousearch for answers to your questions; but youneed to have good, interesting questions to createinteresting projects.

Asking questions is a developed habit.Throughout your school experience, you’veprobably felt like you weren’t supposed to askmany questions. You are supposed to learn. Andif you ask questions, they’d better be good ones.Well, we haven’t begun talking about what makesa question good, but let’s start with someexercises to help us get in the habit of askingquestions.

Accepted wisdom… is… often the opposite ofcritical thinking, which relies on questioning.In many schools, for example, critical thinkersare, if not punished, stifled because of their“disruptive” need to question (and therebychallenge authority).

– From the Community Toolbox,contributed by Phil Rabinowitz

Class Exercise

Ask students to complete the handout below withseven topics that interest them in the science classthey are taking. What questions do they haveabout each? Where would they intuitively searchfor answers to those questions?

Handout: Questioning and Scientific Inquiry

Then collect the handouts and randomly givethem out to other students (no names on this).Have the receiving student:

- Pick the two top questions of most interest tothem and discuss if these questions include theone that the first student thought was mostinteresting.

- Identify what makes the two questions theychose interesting to them.

Questioning And The ScientificProcess = Fun And Surprises

Science should be fun – a creative explorationof the world around us that arises out ofcuriosity. However, it is sometimes difficult,given the standardized testing requirementsand local school board mandates, to conveythe joy of science. Focusing on questioningand ignorance may feel uncomfortable forsome. But our goal is to try to turn inquiryinto fun by allowing students to focus onthings that interest them.

Teacher Information

1. A compilation of brief answers from over 150people, in different fields, about what makes themcurious. Could use any samples of interest.http://curiosity.discovery.com/question/what-makes-you-curious

2. How does it feel to realize you’re wrong?Getting things wrong is fundamental to beinghuman and is deeply related to our creativity. -17.52 minuteshttp://www.ted.com/talks/kathryn_schulz_on_being_wrong.html

Narrative

What do you think makes for a “goodquestion”? It’s important that we try to figurethat out. There’s no right answer. But first, Iwant us to get used to simply askingquestions. I want you to practice thinking, andthinking about things that make you wonder,just like Richard Feynman did. So before we

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…we have turned things around inscience education. We confront studentsfirst with what we call the basics…agreat mass of factual information. Onlylater…do we let them in on the secret thatfacts change…are biodegradable. Wemight be better off by letting the studentsknow what the great puzzles are beforethey learn all the basicinformation-arouse their curiosity, makesure they get sufficiently puzzled aboutnature and then go on. - Lewis Thomas

talk more about the projects you’ll be workingon, let’s talk about questions and their role inscience, because the entire scientific processrevolves around questions, as Lewis Thomasand Nobel Laureate Francois Jacob havewritten about it:

“The game was that of continually inventing apossible world, or a piece of a possible world,and then of comparing it with the realworld.... a race without end... What matteredmore than the answers were the questions...For me, this world of questions, and theprovisional, this chase after an answer thatwas always put off to the next day, all thatwas euphoric. I lived in the future... I hadturned my anxiety into my profession.”

– Nobelist Francois Jacob, The StatueWithin: An Autobiography. Basic Books, NewYork, 1988.

You might enjoy watching a bit of this video,in which people from all walks of life talkabout what makes them curious:http://curiosity.discovery.com/question/what-makes-you-curious

At the beginning of any research project, yourquestions often revolve around, “What’s my

research going to be?” That part of researchis often called the “context of discovery.”You’re thinking, coming up with ideas,finding out which direction to go. The types ofquestions that researchers ask themselves,either explicitly or implicitly, are the sametypes we all ask ourselves when we encountersomething we don’t know or understand:

1. How does that work?2. Why does that happen?3. What if you take this and do that, what

would happen?4. What if I could create X to do Y?

So the context of discovery is simply a fancyname about wondering. Wondering how theworld works and how life works.

Most other questions that arise duringresearch are associated with what can becalled the “context of validation.” We willtalk later about the scientific method, butexamples of questions that arise duringresearch include:

1. Is this an interesting question to test?2. Can I create a test to answer my question?3. Is this a good hypothesis?4. Is this a good test of the hypothesis?5. What if my test supports my hypothesis?

What can I say or claim?6. What if my test doesn’t support my

hypothesis? What can I say or claim?7. What would I do with the knowledge I

gain from the tests?8. Would there be real-world application of

such knowledge?

As obvious as this all might sound, the biggeststumbling block for all of us is getting used toasking questions, “uncorking them,” whetherthey seem simple, complex, obvious, orunanswerable. Many of us don’t want toappear dumb, so we don’t ask what feels likea stupid question or one that we think other

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people probably already know the answer to.

But as we said before, answers are not alwaysfacts. They change all the time. Even withoutknowing much about Albert Einstein’sgeneral theory of relativity, you can probablyappreciate that anyone who asked him thesimple question, “What time is it?” would getan unexpected answer.

Class Exercises

1. Engage students in finding out why people arereluctant to ask questions and the type ofquestions they are reticent to ask.

2. Take the class for a brief walk – outdoors,down the hall, or wherever you can get them intoan environment other than the classroom. Askthem to look at what they see and try to think ofquestions they have never asked themselvesbefore.

Are There Answers And Does ItMatter?

Science is not a substitute for philosophy orreligion. It is a method of learning more aboutthe world we live in, and it is particularlysuited to questions that have some possibilityof being answered. And when answers arefound and applied to real-world issues, theymake a difference in people’s lives.

Teacher Information

1. Physicist David Deutsch discusses why therise of scientific inquiry and understandingtransformed the world within a few centuries.http://www.ted.com/talks/david_deutsch_a_new_way_to_explain_explanation.html

2. Surgeon Peter Attia argues that medicine’scurrent approach to diabetes might be wrongbecause of the assumptions – and the judgmentalattitudes – that underlie the approach.http://www.ted.com/talks/peter_attia_what_if_we

_re_wrong_about_diabetes.html?utm_source=newsletter_daily&utm_campaign=daily&utm_medium=email&utm_content=image__2013-06-25

Narrative

In a while, we are going to talk about whatmakes for a good scientific question forresearch. But first, I want to talk aboutquestions that are not really the domain ofscience-questions that cannot be answeredusing a scientific method or laboratoryequipment. While these are not questionswe’ll pursue in this class, it’s important foryou to keep in mind the type of questions thatare not answerable through the scientificmethod.

| Video Resources

1. Surgeon Peter Attia argues that medicine’scurrent approach to diabetes might be wrongbecause of the assumptions - and the judgmentalattitudes - that underlie the approach.15:58minuteshttp://www.ted.com/talks/peter_attia_what_if_we_re_wrong_about_diabetes.html?utm_source=newsletter_daily&utm_campaign=daily&utm_medium=email&utm_content=image__2013-06-25

2. Questions that no one knows the answers to.12:08 minutes; suggested excerpt: 0:00 - 1:43minutes

http://www.ted.com/talks/questions_no_one_knows_the_answers_to.html

Class Exercises

Divide the class into groups of four. Have eachgroup write up a list of questions and put the onesthey think can be answered by science into a YEScolumn – and those they think cannot be answer-ed by science, into a NO column. Then have theclass review what each group wrote and discusswhy they agree or disagree with the way eachquestion was categorized. Encourage students tointeract with each other as they explain their

thinking and possibly challenge each other.

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What Makes A Question “Good” OrInteresting?

No one metric can easily be used in allsituations for the quality of questions. But onecharacteristic of good questions is that theyengage the student and express a curiosity anddesire to find out more – and when onequestion leads to another and to another. Thismakes it fertile ground for research. In thissection, the goal is to encourage students tofocus on questions that each person isinterested in, rather than a rote assignment.

Teacher Information

1. A guide to asking good questions.EssentialQuestions.pdf; suggested excerpt, page1.http://www.ocmboces.org/tfiles/folder1682/OHS

2. Stephen Johnson discusses what kinds ofenvironments foster unusual levels of creativity. –17:46 minutes (suggested excerpt: 7:20-9:25)http://www.ted.com/playlists/20/where_do_ideas_come_from.html?-

3. A brain surgeon observes, and asks herselfsome interesting questions, as her brain functionsshut down one by one during a massive stroke. –18:42 minuteshttp://www.ted.com/talks/jill_bolte_taylor_s_powerful_stroke_of_insight.html

Narrative

As you can imagine from Richard Feynman’squestion about why the ball rolled to the backof the wagon when he began to pull it, as wellas your own experiences, one good question islikely to lead to another…and another. Nowwe’re going to think about a question thatinterests you, and whether it would make agood research topic.

Go far, stay long, see deep.– Outside Magazine

Class Exercises

1. Ask students what they believe makes for a“good research question.”

2. Ask students to identify a topic they areinterested in. If the class is conducive to a finalproject, this may well be the point to identify theresearch topic they will pursue.

3. Handout: Questioning and My Interests

After collecting the papers, mention that you willrevisit this same exact exercise after your studentsbegin their project. The point is to demonstratethat questions evolve and that the search foranswers often leads to additional questions. Excerpt From SIMI High School StudentSheridan Haskie (pg 19)

Exercises In Questioning

The only way to become proficient at comingup with good questions is to practice. Thissection gives your students an opportunity topractice their questioning skills and discusstheir thinking with each other.

Teacher Information

1. Excerpt from My Cousin Vinny, in which heasks great questions - on Teacher Tube.http://www.teachertube.com/viewVideo.php?title=My_Cousin_Vinny&video_id=119383

2. A blog with clips from TV and movies thatillustrate asking good questions.http://larryferlazzo.edublogs.org/2012/08/04/the-best-videos-showing-the-importance-of-asking-goo

d-questions-help-me-find-more/

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Sheridan HaskieHigh School Student, Class of 2005 (SIMI 2003)Greyhills Academy High School (Tuba City, AZ)

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Narrative

We’ve talked about what doesn’t make for agood research question, which is one thatsimply can’t be answered. And we’ve talkedabout what makes for a good question, whichis something that is potentially answerable

and of interest to you. Without a personalinterest, it is difficult to really becomepassionate about scientific research. Butbefore you finalize your topic for a finalproject, let’s do some exercises to see whatkind of questions might come up if you chosea particular topic.

Figure 3: The Curriculum on Medical and Other Ignorance Activities

Witte MH, A Kerwin, CL Witte: Seminars, clinics, and laboratories on medical ignorance. J.Med. Educ. 63:793-795, 1988.

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Class Exercises

Distribute one of the scenarios (press releases)used in SIMI (e.g., ‘Growing Your Own Organ’)in the Translation Theme section or create a“press release” of your own that is moreappropriate to topics you teach, or have thestudent bring in recent news articles aboutmedical breakthroughs/medical oddities.

What is your overall reaction to the scenario -positive or negative/good or bad? Ask at least 1question in each of 3 categories about thescenario: Type 1: basic science (inner workings ofbody processes or mechanisms of disease), Type2: clinical (about a patient or whole person); Type3 (societal, ethical, legal issues)

Student Project

As we said early on in this outline,constructing a final project that teaches othersis, in our experience, one of the best ways tolearn a topic. We therefore hope that thiscurriculum on questioning leads to a studentproject, whether it’s a science fair or adomain-specific project related to your class.Our focus throughout has been the portion ofscientific method that stresses observation andcreating good, researchable questions.

Teacher Information

We hope that we have provided resources thatwere useful to you as you emphasize theimportance of this first step in the scientificmethod. Information and resources for yourstudents to create a final project are provided atthe close of the second part of this curriculum:Translational Science and the ResearchEnterprise.

Narrative

By now, you know some things that you foundinteresting, and you are learning what makesfor good questions. Maybe you’ve alreadyasked some. So now comes your biggest

chance to turn one of those questions - or adifferent one - into a project that reallyinterests you and that can translate to someissue we face in the real world.

Class Exercises

An outline of the project introduction we usemight be useful to you.

1. Project Preparation – Ask students to trackthe path of their questions and be prepared toanswer:

- What questions did you have at the beginning? - What questions arose as you were researchingthe first questions? - How do you go about looking for answers to thequestions you currently have? - What resources could you use to look foranswers?

2. Observation Exercise – The goal here is notonly for students to accurately describe their closeobservations about an object, photograph,experiment, but to ask several questions based onthem.

3. Background Review for Project – Haveyour students identify seminal readings orwebsites in their area of interest. Their questionsshould include:

- What does the author think he knows? (i.e.,identify the author’s assumptions) - What is the author ignorant of? - What is his/her basic question? - What are you, the reader, ignorant of beforereading the paper? - What are you, the reader, ignorant of afterreading the paper? - What questions were raised by the paper?

4. Focus – What will the student’s project focuson, and what are the questions they start with?

When the scientist tells you he does not knowthe answer, he is an ignorant man. When hetells you he has a hunch about how it willwork, he is uncertain about it. When he is

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pretty sure of how it is going to work, and hetells you, 'This is the way it's going to work,I'll bet,' he is still in some doubt. And it is ofparamount importance, in order to makeprogress, that we recognize this ignoranceand this doubt. Because we have the doubt,we then propose looking in new directions fornew ideas. The rate of the development ofscience is not the rate at which you makeobservations alone but, much more important,the rate at which you create new things totest. – Richard Feynman, The Meaning Of It All

(27)

SIMI Student Reflections OnQuestioning

Quotes from SIMI High School Students:

“This summer I ran upon many questions...questions that got answered, questions thatgot half-answered, and questions that didn’tget answered’.

“Before I began this program, I believed thatasking questions was a form of stupidity. Iwas so nervous and afraid.”

“I never thought of myself as ignorant, butonce I realized it, I began to think on a more

critical plane. I am a better analyzer, but Ineed to write down my questions morebecause I forget them.”

“Until this week, it never hit me how much Ihave begun to use questions in every part ofmy life... Questions keep filling and expandingin my brain like carbonation in a soda canafter it has been vigorously shook. I foundthat the only way to impede the explosion ofmy brain was to write the questions down sothey had somewhere else to exist... I neverwould have guessed that a simple set of dailyworksheets would have impacted my life somuch.”

“I am no longer self-conscious that the levelof ignorance my questions hold will define mylevel of intelligence: they only define myambition to learn.”

“This summer showed me I need to askquestions. I’ve learned that just sitting in theback of the room, taking in all theinformation, is not going to help me; I need tobe in the middle of it all, amid all the action,interacting with the person speaking. We needto investigate things and find what’s real,what’s true.”

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M

The Translational Theme

WHAT IS TRANSLATION?

Translation has a variety of meanings and nuances:

“...the bidirectional process of applying ideas, insights, ad discoveries generated through basicscience inquiry to the treatment and prevention of human disease...” National Institutes of Health

Webster’s dictionary definition:Translation: 1. Rendering of something into another language. 2. A version in a differentlanguage. 3. Change or conversion to another form, appearance, transformation. 4. Act or processof translating. 5. motion in which all particles of a body move with the same velocity alongparallel paths. 6. Retransmitting or forwarding of a message, as by relay.

Biochemistry: “the synthesis of a polypeptide from its mRNA template”

What do the different meanings of translation have in common, how do they differ, and what aretheir implications for each other?

Translational Science And The Research Enterprise

any people are good scientists. They haveasked good questions, they have

stimulated others with interesting research,and their findings are exciting. But scientificresearch often gets stuck in the lab. Why?And how does basic research lead toreal-world situations, like developing newdrugs and understanding illness?

This is our topic in the second part of thiscurriculum. As translational researchers, wetake the basic research we have conducted inour labs and translate it into applications thatbenefit people.

Doing this necessitates a paradigm shift in theway we conceive of the relationship betweenmedical “knowledge” (the known), andmedical “ignorance” (unanswered questionsand unquestioned answers-the unknown) inthe translational process. Today’s students arefaced with mountains of knowledge fromcenturies of research, and they can link to itinstantly. Yet, medicine and science are most

often furthered by those who question andthereby discover.

What has been missing is a program thatamalgamates medical knowledge and student-centered inquiry. Through this curriculum,your students can now simultaneously acquiredifferent kinds of knowledge through theinterweaving of its two modules – this secondone, with its medical/scientific andtranslational concept/content, and theignorance/inquiry modules we began with.

What Is Translational Research?

“Translational research is scientific researchthat helps to make findings from basic scienceuseful for practical applications that enhancehuman health and well-being. It is practicedin the medical, behavioral, and socialsciences. For example, in medicine it is usedto "translate" findings in basic researchquickly into medical practice and meaningfulhealth outcomes. Applying knowledge from

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basic science is a major stumbling block inscience, partially due to the compartmen-talization within science. Hence, translationalresearch is seen as a key component tofinding practical applications, especiallywithin medicine.”

(Wikipedia)

“Clinical and translational science are fieldsdevoted to investigating human health anddisease, interventions and outcomes for thepurposes of developing new treatmentapproaches, devices, and modalities toimprove health. New molecular tools anddiagnostic technologies based on clinical andtranslational research have led to a betterunderstanding of human disease and theapplications of new therapeutics for enhancedhealth.”

– D Robertson and G Williams, Clinicaland Translational Science: Principles ofHuman Research, Copyright 2009 ElsevierInc.

Translational research is also sometimesreferred to as “bench to bedside.” In medicine,this is where basic science research andclinical medicine interface – such as the longresearch that translated the curiousphenomenon of mold in a petri dish into thewonder drug that penicillin became, whichforever changed medicine and has savedcountless lives.

But translation often occurs in the reversedirection – “bedside to bench and backagain,” such as the observation in patientswith bacterial (pneumococcal) pneumonia thatthe “information” programming virulence ofthe smooth encapsulated form of thePneumococcus was contained in a sugarmolecule (DNA) and not a complex protein.This revolutionary bedside to bench discoveryin 1944 of the “transforming principle” andthat genes are made of DNA precededelucidation of the double helix structure ofDNA by nearly a decade and the beginning ofits full bench to bedside applications in theHuman Genome Project 50 years later.

McCarty, M: The Transforming Principle:Discovering that genes are made of DNA.1985Watson, J: The Double Helix. 1968.Atheneum

Other examples of Basic Science Implicationsof Clinical Observations, such as the dietarycure of pernicious anemia which led to thediscovery of vitamin B12 (cobalamin) and itsphysiologic role, can be found in a series ofoccasional articles under this title in the NewEngland Journal of Medicine.

H. Franklin Bunn, MD: Vitamin B12 andPernicious Anemia - The Dawn of MolecularMedicine. NEJM 370: 773-776, 2014

Figure 4. T1= Basic Scientific Discovery and Translation to Humans, T2=Translation toPatients, T3=Translation to Practice, T4=Translation to Populations.

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Translational biomedical research wasoriginally divided into 2 categories: T1research, the “bench-to-bedside” enterprise oftranslating knowledge from the basic sciencesinto the development of new medicaltreatments; and T2 research, translating thefindings from clinical trials into everydaypractice. This scheme has recently beenexpanded into 4 categories on a continuum(Fig. 4).

Here, we discuss translational research fromthis medical point of view, including therelated political, financial, and public healthissues involved.

Teacher Information

1. “What Is Translational Research and Why DoYou Think it is the Way to Achieve BetterClinical Results?” – Eric Rose, M.D., chairman ofthe Department of Surgery, Columbia UniversityMedical Center, discusses translational research.http://www.cumc.columbia.edu/publications/in-vivo/vol4_iss1_mar_apr_05/translation_research.html

2. “The Meaning of Translational Research andWhy It Matters” – from the Journal of theAmerican Medical Associationhttp://jama.jamanetwork.com/article.aspx?articleid=1149350

3. A Historical Perspective on Clinical Research– from the ancients to the 20th century – is concisely presented in Principles and Practice inClinical Research by John Gallin, AcademicPress, 2002, pp 1-11.

4. Another historical and fascinating source isClassical Descriptions of Disease which representthe original descriptions by the physicians whorecognized these disorders and their thinkingabout mechanisms, tools, and management as wellas manifestations.

Ralph H. Major: Classic descriptions of disease;with biographical sketches of the authors, With127 illus. Springfield, Ill., C. C. Thomas, 1932.

Narrative

Somewhere along the way, many of us havecome across the idea that basic research isthe source of true discovery – probing thevery nature of the world, from particle physicsto cosmology – whereas applied research isnot “real” research. Instead, appliedresearch is often considered to be similar towhat engineers do: design things, make them,fix them (even this view of engineering islimited). But this distinction between basicand applied research can mistakenly beessentially a class perception of intellectualsuperiority.

| Video Resources

1. A good overview of translation from anemotional/human perspective – a promotionalvideo for The Altman Clinical and TranslationalResearch Institute at the University of Californiaat San Diego. – 5:58 minuteshttp://www.youtube.com/watch?v=2EAJV9I4r7g 2. Career Girls: Physician/Scientist“Translational Research” (part of the Career Girlsongoing series of career guidance/ inspirationvideos.) – 1:38 minuteshttp://www.youtube.com/watch?v=xcDLdMYb1jg (See more at http://www.careergirls.org)

3. Basic and translational research are bothimportant to the advancement of humanknowledge, but they work in different ways andhave different end goals.http://www.wisegeek.com/what-is-the-difference-between-basic-and-applied-research.htm

4. Article /advertisement on what translationalresearch is, and the many occupations that areways to engage in it.http://www.labanswer.com/translational_research_laboratories.asp?gclid=CI_n4IXM0rkCFQie4AodkRIAOQ

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[Nobel laureate] Sydney Brenner is one of many scientists challenging the ideathat translational research is just about carrying results from bench to bedside,arguing that the importance of reversing that polarity has been overlooked. "I'madvocating it go the other way," Brenner said. Bedside to bench means that clinicaltrials and patients' unexpected responses are valuable human experiments, andfailed trials can stimulate new hypotheses that may help refine the experiment in itsnext iteration.

– From http://www.nature.com/news/2008/080611/full/453843a.html

Class Exercises

1. Have students think of examples ofmedical treatments, or procedures such as theflu vaccine or x-ray visualization. Then havethem trace their probable development fromthe lab and observations.

2. Ask them to pick a historical period thatinterests them and find out how scienceadvanced our common humanity at the time.How did it probe and push the boundaries ofwhat was possible then?

3. Explain some new technologies tostudents and then have them come up withapplications for them. Also, have them tracehow the technologies were discovered. Agood example is polymerase chain reaction(PCR).

Examples Of Translational Research

How penicillin became the wonder drug itdid, and transformed medicine is, as wementioned, a shining example of translationalresearch. It is also a wonderful example of theway that teamwork and collaboration produceresults that would not otherwise occur. Wewill use it for some of the class exercisesgoing forward in this part of the curriculum.Other examples mentioned above includediscovery of DNA as the “transforming

principle” and Vitamin B12 treatment ofpernicious anemia.

“The Meaning of Translational Research: theStory of Penicillin”http://www.ox.ac.uk/research/medical_sciences/projects/penicillin.htmlhttp://ctb.ku.edu/http://ctb.ku.edu/en/tablecontents/sub_section_main_1120.aspx

You'd be hard pressed to find an advance inalmost any area of humanity's developmentthat didn't start with someone looking at theway things were and saying "It doesn't haveto be that way. What if we looked at it fromanother angle?"

– The Community Toolbox

Teacher Information

1. Background information on encouragingstudents to formulate questions. See earliersection on questioning.

Resource

2. Drug Discovery

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Narrative

How penicillin evolved from AlexanderFleming’s 1928 observation of mold growingin a petri dish to become a revolutionary drugthat forever changed medicine and savedcountless lives, is a wonderful example oftranslational research. Fleming, a biologist,pharmacologist, and botanist, noticed anempty spot in the center of a bacteria-culturedpetri dish where something grew that waskilling off the bacteria. He named it“penicillin” and continued to investigate itfor about a year, but stopped because it wastoo difficult to grow and store.

Two other men, who realized that the oddsubstance had medicinal properties and wereprompted by the widespread battlefieldinfections then being seen in World War II tocontinue their investigations, but theycouldn’t find a way to produce sufficientamounts of it to test it. However, a laboratoryhad begun to investigate penicillin on a smallscale, and the two men eventually took overthe lab and initiated penicillin’s transitioninto the medical setting by experimenting withrats, and eventually with humans.

The watershed advance in medical sciencethat penicillin came to represent, as the firstlaboratory-produced and controlledantibiotic, began as basic research - just ashappens with other drugs and biomedicaldevices. And the story of penicillin illustratesboth areas of translational research: (1)applying discoveries generated by laboratoryresearch to preclinical studies and clinicalstudies in humans; and (2) translating thefindings of clinical trials into everydaypractice.

The bottom line is that penicillin only becamethe revolutionary drug it did becausetranslational research made it happen.Otherwise, it would have stayed in the lab.

| Video Resources

Bedside to bench – Nature recounts three storiesin which results from human experiments inspirednew avenues of research.http://www.nature.com/news/2008/080611/full/453843a.html

The emerging paradigm (with many historicalexamples) in biomedical research termed –“translational research” – focuses on iterativefeedback loops between the basic and clinicalresearch domains to accelerate knowledgetranslation from the bedside to the bench, andback again.http://en.wikipedia.org/wiki/Medical_research

Class Exercises

1. Ask your students to think about people theyknow (including themselves) who have beentreated with penicillin, and the varieties ofmedical issues for which they were treated. Didpenicillin work? Did they need to changeantibiotics? What was their experience like? Wasit easy to take, or could it have been improved insome way? Did anything happen to anyone thatmight have been useful for researchers to know?Why do they think that so many other antibioticshave been developed since penicillin came intobeing?

2. Encourage your students to come up withsimilar examples in history or select currentevents “ripped from the headlines” and then havethem list their Type 1, 2, and 3 basic, clinical andsocietal (ethical, legal, social) questions at thebeginning of their research on the topic and at theconclusion. A follow-up exercise could be havingthe opportunity to interview an expert on thetopic, pose their unanswered questions, and alsoelicit the unanswered questions on the topic fromthe expert. The student then might also explorewith the expert how some of these questionscould be answered and what research tools mightbe used.

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Science As A Social Activity

Unlike the popular view of scientificresearchers working alone in their labs,scientific research involves teamwork. No oneindividual has all the expertise required forthe full exploration of a project. So thissegment stresses the importance of teamworkand collaboration in conducting research, andapplies this concept to the kids in your class,and the work and projects they undertake.

Translational research requires skills andresources not usually available in a singlelaboratory or clinical setting.http://www.labanswer.com/translational_research_laboratories.asp?gclid=CI_n4IXM0rkCFQie4AodkRIAOQ

Teacher Information

1. Video on the importance of creatingenvironments that foster innovation and goodideas. 17:46 minuteshttp://www.ted.com/playlists/20/where_do_ideas_come_from.html

2. How teamwork produced penicillinhttp://www.ox.ac.uk/research/medical_sciences/projects/penicillin.html

3. Videos by the Industrial Research Institute onits tournaments and programs to promoteinnovative research and developmenthttp://www.iriweb.org/

4. A diagram of the work cycle and theinterconnections between its elementshttp://www.iftf.org/fileadmin/user_upload/images/More_Projects_Images/TH-FutureofWork.jpg

5. Enhancing Collaborative Communication inTranslational Climate Sciencehttp://www.cals.uidaho.edu/toolbox/pres/ORourke2.pdf

Narrative

When you think of a scientist, you probablythink of somebody wearing a white lab coatand working alone in their lab, studying aspecimen or pouring something into a testtube. At least, that’s a common stereotype ofwhat scientists look like and how they work.But the truth is that scientific research is ateam activity. No one person has all thetraining and specialized skills needed to carryout a research project, so researchers withdifferent areas of expertise are needed towork together on the same problem. As yousaw, the development of penicillin was anexample of this, and there are endless othersthat we know about, and don’t yet knowabout. You might be surprised to find yourselfinterested in some particular aspect of such agroup development process.

We like to think of exploring in science as alonely, meditative business, and so it is in thefirst stages, but always, sooner or later,before the enterprise reaches completion, aswe explore, we call to each other…

– Lewis Thomas, Lives of a Cell

Class Exercises

1. Divide the class into groups of five andask them to pretend they are working togetherto find ways to improve penicillin, based onthe experiences with it that emerged duringtheir last exercise. What could make it better,from its capabilities to the way it is taken?Encourage your students to really play withthis and have fun!

2. After the exercise, ask them what theyliked about the exercise and what wasdifficult for them-if anything.

3. Have them watch at least the first twovideos below and discuss theirreactions/thoughts.

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| Video Resources

1. The importance of creating environments thatfoster innovation and good ideas. 17:46 minuteshttp://www.ted.com/playlists/20/where_do_ideas_come_from.html

2. Breakthrough to Cures Games for Change is aglobal organization for games that can make areal-world positive impact. 4:17 minuteshttp://info.breakthroughstocures.org/ See more at:http://info.breakthroughstocures.org/#sthash.DdIiYcrs.dpuf

3. Videos and information by the IndustrialResearch Institute on its tournaments andprograms to promote innovative research anddevelopmenthttp://www.iriweb.org/

4. A diagram of the work cycle and theinterconnections between its elementshttp://www.iftf.org/fileadmin/user_upload/images/More_Projects_Images/TH-FutureofWork.jpg

The Research Enterprise

Research is conducted in both academic andcommercial spheres, and both require funds.We have discussed the academic sphere, andnow we need to address the support systemsand businesses that are essential to completingand implementing the translation process.That’s where “the rubber meets the road,” andthere are many needs for people to work inthese areas of development. For example,biomedical equipment and materials areneeded, as is logistical support. Legal supportis needed to ensure that federal guidelines fordevelopment, testing, and distribution areproperly met; lab technicians are needed totest the new drugs; marketing and sales areneeded to get them to the consumers who canbenefit from them. Without all of theseparticipants and more, the best lab research inthe world will stay in the lab.

Also, some of your students might enjoygaming. If they do, we encourage you to letthem watch the videos below, which utilizegaming skills and engage the gamingcommunity in unconventional thinking thatcan translate into biomedical advances andother solutions to world problems. Thesegames take place from time to time, and yourstudents can participate at no cost. It is a veryexciting enterprise that involves interactionwith a different kind of community. The bestideas generated will be made publicafterward, so we also caution your students tonotice their good ideas and think about howthey want their ideas to go out into the world.

The training takes longer, but those willing toinvest extra time in getting to grips with bothbasic and clinical research can reap thebenefits, not least in job satisfaction, saysKaren Kreeger.http://www.nature.com/naturejobs/science/articles/10.1038/nj6952-1090a

Teacher Information

1. The changing role of pharmacists within themedical community - 18:27http://www.youtube.com/watch?v=QnCGD05u58k&list=PLsRNoUx8w3rNv76zb5fXbng-dVNsN90BI

2. A brief description of the difference betweenbasic and applied research, and how the lines canblur. http://www.wisegeek.com/what-is-the-difference-between-basic-and-applied-research.htm#didyouknowout

3. TED Talk about how gamers and gameplaying can lead to solving some of the world’sbig problems. – 20:32 minutes; suggested sample:5:00 minutes to end http://info.breakthroughstocures.org/?page_id=7

4. This article, from the Myelin RepairFoundation, relates to the gaming video above,and describes how gamers forecast the use ofadvanced data mining to accelerate medicalresearch, among other things. http://info.breakthroughstocures.org/wp-content/u

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ploads/2011/01/BTC-Final-Report-Release-01-31-2011.pdf

Narrative

Do you ever wonder how researchers find orcreate new medicines, or figure out how theywork? It’s not only exciting for them – it canbe life-changing for patients suffering fromdiseases and medical conditions. That’s anextremely rewarding and powerful incentivefor anyone who wants to make a difference inthe lives of others, and the process of gettinga new product from discovery throughdevelopment, testing, approval, packaging,etc., involves many phases and provides manyopportunities for involvement and for jobs,even if you are not a scientist.

For example, biomedical equipment and

materials are needed. Legal support is neededto ensure that federal guidelines fordevelopment, testing, and distribution aremet; lab technicians are needed to test newdrugs; marketing and salespeople are neededto get them to consumers who can benefitfrom them; pharmacists are needed todispense them if they are not sold over thecounter. Without all of these participants andmore, the best lab research in the world willstay in the lab. So, as you move along in thisclass, see if this side of the translationalprocess interests you, and if so, what part youparticularly like. The diagram below showsthe process that’s involved in translatingbasic research into medical products thatenter the marketplace and end up on theshelves of places like Walgreens, where theycan help people.

Figure. 5. Diagram excerpted from http://www.labanswer.com/translational_research_laboratories.asp?gclid=CI_n4IXM0rkCFQie4AodkRIAOQ

Class Exercises

Ask the class to get into groups of six. Thistime, have them assume different roles – from

lab technicians to patent lawyers topharmaceutical reps to marketing andsalespeople – whatever they’d like to be – asthey brainstorm ways to get penicillin to get to

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the point where it can be mass-produced andintroduced into today’s marketplace, as if itwere a brand-new drug. What would theyneed to do? How would they market it, etc.?Let them assume whatever role they prefer – even if two people want to play the same role,and even if someone wants to change theirrole in mid-stream – and imagine how theywould engage in the process.

| Video Resources

1. This article, from the Myelin RepairFoundation, relates to the video on gaming listedabove, and describes how gamers forecast the useof advanced data mining to accelerate medicalresearch (among other things). http://info.breakthroughstocures.org/wp-content/uploads/2011/01/BTC-Final-Report-Release-01-31-2011.pdf

2. Breakthrough to Cures Games for Change is aglobal organization for games that aims to make apositive impact on real-world problems. 4:17minuteshttp://info.breakthroughstocures.org/ See more at:http://info.breakthroughstocures.org/#sthash.DdIiYcrs.dpuf

3. Summary of the ideas that came out of thegames conducted by Breakthrough to Cures -hosted by the Myelin Repair Foundationhttp://info.breakthroughstocures.org/wp-content/uploads/2011/01/BreakthroughstoCures_GameSummary.pdf

How External Factors Can AffectTranslation

Teacher Information

External factors can profoundly re-order thepriorities that an agency or a nation assigns to afield of inquiry, or to a particular type of researchtaking place within a field of inquiry. Thesefactors include social, environmental, financial,and political events, as well as epidemics (such asHIV/AIDS, swine flu) and other extreme

health-related circumstances. Just as the incidenceof battlefield infections during World War IIpushed the creation of penicillin, external eventscan evoke a need for swift solutions and canprompt a heightened response and investment onthe part of agencies such as governments,pharmaceutical companies, private-sector fundingsources, etc., in the search for cures or preventivemeasures such as vaccines.

Conversely, a perceived absence of serious andimmediate need can result in less interest and amore difficult time obtaining resources forresearch, even if the need is real. And, as thesecond resource below states, “political shifts,new legislation, new or modified regulations,global economic conditions, and changes intechnology” can affect what gets researched – ascan societal priorities in relation to human factorssuch as gender, ethnicity, race, age,socioeconomic status, etc.

1. How World War II affected the developmentof penicillin and other medical advances.http://www.historylearningsite.co.uk/medicine_and_world_war_two.htm

2. This article is off-topic, but it clearlydescribes the external factors that affect research.http://www.cdc.gov/niosh/nas/mining/pdfs/whatdoes-externalfactors.pdf

3. “Transforming Clinical Research in theUnited States: Challenges and Opportunities:Workshop Summary” – from the National Centerfor Biotechnology Informationhttp://www.ncbi.nlm.nih.gov/books/NBK50888/

4. Short article from European CancerOrganisation about external barriers to effectivecare in clinical research. http://www.ecco-org.eu/Global/News/EBBC8-News/2012/03/23_03- NEWSLETTERExternal-barriers-to-effective-care-in-clinical-research.aspx

5. Examination of challenges to the adoption ofInternet-based technologies by healthcareorganizationshttp://www.ncbi.nlm.nih.gov/books/NBK44715/

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Narrative

When societies are faced with large-scaleproblems, the need for solutions becomesacute. At such times, resources tend tobecome available to enable researchers tosolve the problem, and projects aimed atsolutions are energized. Just as battlefieldinfections during WWII pushed thedevelopment of penicillin, nuclear energy andlater nuclear accidents spawned a growinginterest in understanding radiation-basedillnesses and finding treatments and potentialcures for them. Likewise, flu epidemics, themeteoric rise in the incidence of HIV/AIDS,and growing prevalence of heart disease haveled to a pressing need for solutions, fromvaccines and the development of newmedications to hardware such as pacemakersand plastic valves.

In short, external factors often play a majorrole in determining what research projectsreceive attention and funding. And it worksboth ways: A perceived absence of seriousand immediate need can result in less interestand a more difficult time obtaining resourcesfor research, even if the need is real. Inaddition, political shifts, new legislation, newor modified regulations, global economicconditions, and changes in technology canaffect what gets researched - as can societalpriorities in relation to human factors such asgender, ethnicity, race, age, socioeconomicstatus, etc.

For example, if you belong to a group that isespecially hard hit by some particular disease– or essentially “owns” that disease, as in thecase of African Americans and sickle-cellanemia – and your group is not prioritized bythe society you live in, you are much lesslikely to get the attention and the resourcesneeded to find a solution to your medicalissue. (One possibility might be to participatein devising a game that draws people to yourcause).

Class Exercises

Have students discuss examples they know ofwhere research or inquiry has been devoted tofinding a cure for something – and caseswhere they saw a need but witnessed a lack ofconcern and public interest. Keep this aspersonal as possible.

| Video Resources

A good overview of translation from anemotional/human perspective - a promotionalvideo for The Altman Clinical and TranslationalResearch Institute at the University of Californiaat San Diego. – 5:58 minuteshttp://www.youtube.com/watch?v=2EAJV9I4r7g

Student Project Resources

One vehicle for learning and communicatingthat learning which we have foundparticularly useful during the SummerInstitute on Medical Ignorance (SIMI) is theassignment of a final project. All of theseprojects require an oral presentation in whichthe student describes their initial questionsabout the topic of their choice; an explanationof the research they conducted, based on thosequestions; and the questions the studentdiscovered waiting for them as they pursuedthe questions they began with. Examples ofstudent presentations can be viewed below.

In addition to the capstone presentation, allhigh-school and undergraduate students(medical students also participate in thesummer institute) are required to produce avideo that teaches others what they havelearned about a research tool or technique.This exercise encourages students to work ontheir communication skills, so they are betterprepared to share their findings and questionsas they become engaged in scientific researchor any aspect of the translational process.Some of the resources available to SIMI

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students are listed below, and they might behelpful for you to use in appropriate settings.

Student Resources

1. Video production assignment2. http://www.medicalignorance.org/progress/handouts/Video%20Project.pdf3. Creating an effective visual presentations 4. Capstone oral presentation handout5. http://www.youtube.com/watch?v=RQaW2bFieo8

Exercises In Translation:

Scenarios

Research topics can be found in news storiesin the daily paper, on TV news, and online.These real world reports can serve asinspiration for asking questions, as well asquestioning the veracity of the reporting, andof the research itself.

Instructions

1. Take 5-7 minutes to read and study thispress release and then list your questions.

2. Did you have a positive or negativereaction to the press release? (check one)

Q PositiveQ Negative

3. List one question you have about thispress release in each of the followingcategories. (please put a check mark next toyour best overall question):

BASIC BIOLOGY (underlying what wasdone and implications)

CLINICAL PRACTICE (diagnosis,management, treatment)

ETHICAL, LEGAL, MORAL ISSUES

Scenario Topics

These scenarios have been created to be ‘almost believable’ but certainly will evoke questionsand consideration.

Grow Your Own OrganPRESS RELEASE

MEDICAL BREAKTHROUGH!: January 1, 2018UMC Surgeon Performs 1st “Grow Your Own” Organ Implant

A 3-month old baby girl dying from a rare metabolic liver disease received the gift of a new liverfrom her mother. Sources revealed that two months ago, a golf-ball sized portion of her mother’sliver was removed and subsequently “grown up” in tissue culture to a normal infant size inpreparation for the historic operation. Last night, the infant’s failing liver was subtotally removedand the “made to order” new one implanted in its place. UA surgeons and basic scientists predictthat this approach may be used to produce a whole variety of new “grow your own” organseliminating the need for donors and harmful anti-rejection drugs. Anybody need an extra leg?

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Bird Flu

Bioterrorism Suspected in Arizona and Mexico, As Bird Flu Outbreak Threatens Lives, Profits

TUCSON, Ariz., Nov. 15, 2017 – Arizona public health officials announced that 10,000 chickenswill be slaughtered today in southern Arizona and northern Mexico to prevent the spread of birdflu.

But infectious disease experts and scientists from the U.S. Department of Homeland Security,puzzled about why this region has been hit so hard and where the virus came from, areinvestigating the possibility that the virulent flu outbreak is the result of a bioterrorist attack.

Four birds on a farm near the Arizona-Mexico border tested positive Monday for a strain ofthe H7 virus that state officials said, as far as they knew, did not transfer to humans. Various birdspecies in the Arivaca Cienega and Madera Canyon bird sanctuaries popular with birdwatchersare being tested.

Janelle D. Flyaway, director of the Arizona Department of Health Services, said the strainfound in Arizona and Nogales, Sonora, Mexico, is different from a mutation of H5N1 avianvirus. The A (H5N1) strain, which scientists believe is a mutation of a bird flu virus implicated inearlier Asian outbreaks, also caused the most recent epidemic in Asia, killing at least 18 peopleand necessitating the destruction of millions of chickens.

The human cases, with a few exceptions, were believed to have resulted from direct contactwith infected chicken, said Flyaway.

To date, 28 human cases have been identified, with fatalities primarily in Vietnam. Othercountries affected are Cambodia, China, Indonesia, Japan, Laos, South Korea and Thailand,according to the U.S. Centers for Disease Control. CDC scientists said no vaccine is available toprotect humans against the deadly strain of avian

Gene to cure baldness

Biotech Company Claims Breakthrough: New Gene Expression Technology Could Control Cancer, Cure Baldness

NEW YORK, N.Y. April 5, 2018 - SUPERGENIX, a recently launched biotech company, wentpublic today offering shares on the New York Stock Exchange, as it announced approval of itspatents to cure male-pattern baldness and perform other marvels.

Myra T. Bushy, vice president for communications, said SUPERGENIX’s breakthrough newtechnology will turn genes on and off.

“The prospects for enhancing athletic performance, growing hair, and evading airport securityby promoting or silencing master genes and target genes, are truly mind-boggling, she said.”

Bushy also noted that FDA approval is not required to market the new gene profiling andmodification technology, based on extensive animal studies. The new methods will also enablescientists to alter pigmentation, changing hair and skin color, and to correct disease-causingmutations. In addition, the new therapies will be applicable to diseases such as cancer andcongenital anomalies, where regulation of cell growth is a major problem.

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Obesity

Federal Government to Subsidize New Obesity Drug

WASHINGTON, D.C., Jan. 2, 2017 – Dan D. Mann, secretary of health and human services, isurging the U.S. Food and Drug Administration to expedite the approval of a new obesity drug,Lipex, developed with funding from Merlox, Inc., the pharmaceutical giant. Mann promised thatthe federal government will subsidize all prescriptions of the drug in an effort to curb the growthof what he calls “one of the gravest public health threats to Americans today.”

In light of the recently announced standards for ideal weight and height, Lipex promises tobring the national rates of obesity down by as much as 50 percent in the next five years, savingtax payers up to $39 billion a year-or about $175 per person, according to a study by the Centersfor Disease Control and Prevention.

Currently nine million children are obese, two out of every three adults are overweight orobese, and 300,000 die annually of obesity-related conditions, including Type 2 diabetes,cardiovascular disease, some cancers and gallbladder disease.

Cancer Vaccine

Potent Cancer Vaccine Ready for Clinical Trials

WASHINGTON, D.C., June 19, 2016 – The U.S. Food and Drug Administration has approvedclinical trials for a potent new cancer vaccine, CVAX, that uses the patient’s own white cells toattack and destroy the malignancy. In high-risk patients, the vaccine is designed to preventmalignancies from forming in the first place.

Federal scientists, along with physicians and biomedical scientists at the in Boston and NewYork City, will begin the efficacy study immediately of 1,000 patients suffering from advancedstage breast cancer and melanoma.

An additional 50 patients will be included with a strong family history of breast cancer ormelanoma who have not yet developed the disease.

The vaccine incorporates the patient’s own genetically altered cancer cells to help the bodyrecognize them as cancerous; the body’s immune system, particularly the dendritic cells, caninitiate the immune process.

A government spokesman, Hoff Rubocin, said the teams hope to have a vaccine ready formass distribution within three years. If successful, said Rubocin, echoed by patient advocacygroups, “This could truly be THE cure for common cancers.”

Further Exercises

1. Return to the scenarios in the Questioningsection. Now look at each from theperspective of translation and incorporateyour basic, clinical and societal questions intothe analysis. What basic science discoveriespreceded the medical breakthrough? Whatsources will you use to find out? What

challenges faced the discoverers before theycould apply the findings to the breakthrough?Also, students can select their own “medicalbreakthrough” from the current print media orinternet and perform a similar analysis.

2. Have the students pick a common or raremedical disorder of interest to them and askthem to pursue the historical sequence of

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research that led to understanding of thedisorder. A valuable resource is Goodfellow,J, ed: Understanding Medical Research: Thestudies that shaped medicine. WileyBlackwell, 2012. In this compendium, leadingmedical researchers in 8-13 pages eachidentify 10 primary research papers (quotedexcerpts) that have “shaped the direction ofresearch in their given topic, examining whythey were carried out, key findings and howthey changed the field, and ending with keyoutstanding questions, key research centers,and additional references. Topics coveredrange from heart failure, asthma, AIDS, and

stroke to epilepsy, migraine, inheritedhemoglobin disorders, rheumatoid arthritis,and the biochemistry of depression.

To integrate with the Questioning Theme ofthe curriculum, they can begin with listingtheir starting questions and end with thequestions that remain unanswered or newones that have arisen during their readings orreflection. The final product could be awritten report, oral presentation or even avideo, which might be suitable for inclusionon the VCRC/Q alongside one by a medicalexpert on the same or related topic.

SIMI Student Reflections On Translation And Relation To Questioning

“ My question process has become more streamlined. My basic science questions seem to bleedinto my clinical questions which then seem to connect to the social questions.”

“SIMI taught me that asking questions is the only sure way to understand a subject. I havelearned to think about questions from multiple lenses (basic science, clinical and ethical) andhave thought about future topics to explore in my lab research from these three perspectives.”

“The initial questions I’ve had contained more basic biology type queries than all the othercategories. However, after learning more about all of these basic processes, I feel like myquestioning has shifted more to how this basic biology could be applied to real world situationsand diagnoses.”

“I am starting to consider what about the topic is useful instead of what the topic is itself.”

“I began to ask more complicated questions and found more connections between the research Iwas doing which was more of a public health topic and the clinical implications and basicsciences.”

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W

Overview of Evaluation

Keep in mind that the primary desired outcome and reward system of the TT/SQ Curriculum isstudents engaged in questioning and thinking about their thinking (more curious) as well asunderstanding the scientific process and translation. Students will not only be more science andhealth “literate” but many will choose medical/health science careers. Rewards should bestructured according to these desired outcomes.

e recommend using the logic model andformative assessment, both of whichare defined below, as a means to assess

the progress your students have made.

The Logic Model (Fig. 6)

A logic model is a diagram that illustrates therationale behind your program. It shows therelationships between the resources you invest(inputs), the activities you carry out (outputs),and the benefits you expect (outcomes).

You can read a logic model as a series ofif/then statements that connect the differentcomponents of your program. For example:

If we have resources (inputs), we can carryout activities (outputs).(e.g., If we have funding for staff andappropriate materials, we can carry out afterschool EE programs.)

If we carry out activities (outputs), we createchanges in participants (outcomes).(e.g., If we carry out after school EEprograms, students’ environmental literacywill increase.)

(Adapted from W. K. Kellogg Foundation,2004)

A logic model displays the sequence ofactions that describe what a program is and

will do – how investments link to results. Thefive core components in a logic model are: INPUTS: resources, contributions,investments that go into the course orprogram;

OUTPUTS: activities, services, events andproducts that reach people who participate orwho are targeted;

OUTCOMES: results or changes forindividuals, groups, communities,organizations, communities, or systems;

ASSUMPTIONS: the beliefs we have aboutthe course or program, the people involved,and the context and the way we think theprogram will work;

EXTERNAL FACTORS: the environmentin which the program exists includes a varietyof external factors that interact with andinfluence the program action.

The logic model is used in planning,implementation, evaluation andcommunication. While the term “program” isoften used, a logic model is equally useful fordescribing group work, team work,community-based collaboratives and othercomplex organizational processes as we seekto promote results-based performance.”

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Figure 6. Logic Model Diagram. http://meera.snre.umich.edu/plan-an-evaluation/step-2-clarify-program-logic

http://www.wkkf.org/resource-directory/resource/2006/02/wk-kellogg-foundation-logic-model-development-guide

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Formative Assessment

Formative assessment is a process used byteachers and students during instruction thatprovides explicit feedback to adjust ongoingteaching and learning to improve students’achievement of intended instructionaloutcomes. Formative assessment is a methodof continually evaluating students’ academicneeds and development within the classroomand precedes local benchmark assessmentsand state-mandated summative assessments.

Teachers who engage in formativeassessments give continual, explicit feedbackto students and assist them in answering thefollowing questions:

1. Where am I going?2. Where am I now?3. How can I close the gap between the two?

In order to show students how to close the gapbetween where they are academically andwhere they want to be, teachers must helpstudents evaluate their progress in the learningprocess and give them explicit, descriptivefeedback specific to the learning task.

From: Heather Coffey, Learning NC,University of North Carolina at Chapel HillSchool of Education, copyright ©2009.http://www.learnnc.org/lp/pages/5212

SIMI and TT/SQ CurriculumInstruments Used (available foradaptation to your classroom)

• Pre-post Attitudes toward ignorancesurvey

• Pre-post Questions about 5 MedicalTopics

• Comparison of Week 1 and Week 6Ignorance Logs

• Final Course Evaluation• Mentor Evaluation of Student

Performance• Portfolio of student products: Final oral

presentation, Final written report,Research tool video, other

• Follow-up evaluation: Continuingeducation, career pathway, furtherresearch, honor and awards, leadership,presentations and publications, mentoring,community activities.

• Annual survey

Toward An “IQ3" (Insights fromSIMI):

Q3 scale (derived from studentself-assessments) – Pilot measure of studentprogress in questions, questioning, and asquestioner - under study and validation:

Questions: Dimensions - breadth, depth,variety (multiple perspectives), content (whatvs how/why), content (basic vs. applied),open/closed (tractability). Data sources:scenarios, question logs, self-assessment Questioning (Process) - Dimensions: speed,volume (character counts), number ofquestions, connectivity/linkage vs. chaotic.Data source: Self-assessment, question logs,scenarios.

Questioners: Dimensions – Shyness/fear/embarrassment/discomfort vs. confidence/comfort; curiosity/joy/discovery; skeptical;value of questioning; humility; thoughtful.Data source: self-assessment, question logs,scenarios.

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TRANSLATING TRANSLATION ANDSCIENTIFIC QUESTIONING

CURRICULUM: PUTTING IT ALLTOGETHER WITH YOUR SIGNATURE

Figure 7. Translating Translation Core Curriculum.

A suggested sequence for the TT curriculum(Figs. 7) begins with the Questioning Themeand Introducing Medical Ignorance, evokingexamples of each from the students followedby using some of the resources suggested oryour own that parallel those presented. It isimportant to recruit the students to find theirown examples from their personal life, family,or media sources. But most crucial of all,begin and continue, and end with some way touncork student questions – handwritten,e-mailed, mobile phone access, so they remaincontinually active questioners. And have themframe their assignments with beginning andending questions. Make sure to providerewards and credit for the studentsquestioning and progressing.

Then move on to the Medical VocabularySection which is a sequence on the Nature ofDisease developed by UA PathologyProfessors Ronald Weinstein and AnnaGraham for high school level students. Thesehave been adapted to the TT curriculum byincluding only 4 sessions on the Nature ofDisease – Classification, Necrosis,Inflammation, and Neoplasia.

With this basic medical vocabulary nowfamiliar, students can then expand theirexploration of medical ignorance and take on

the subject of translation – continuing toframe their exploration with beginning andending questions – basic, clinical and societal(paralleling the translational process). A“brain on-hands” on biomedical researchexperience would be optimal, if only for abrief few weeks or even a site visit or anadventure on the VCRC/Q with one of thefeatured researchers – a professional or aSIMI student – can then be the springboardfor more questioning and a deepeningunderstanding of the translational process.This is further reinforced by the scenarios,historical vignettes, variety of videos, andreadings that illustrate the translationalprocess – the promise and challenges – inmedicine. Iterative questioning is the vehicleand exploration in the Questionarium is thecontinuing process that is designed to beengaging and curiosity-provoking for thestudents, luring them into science’s mysteries.

The TT/SQ Curriculum can be delivered in a“high octane” form, “low octane,” or “self-serve,” remembering that launching thestudents into their questioning journey –“uncorking” their questions/curiosity – is thecrucial strategy – the sine qua non – for“engagement” and capturing the thrill andwonder of real science.

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EPILOGUE

on voyage in your exploration of the worlds of Ignorance, Questioning, and Translation andkeep in touch...

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