Dolan DNA Learning Center Annual Report 2006 Corporate Advisory Board Established in 1992, the Corporate Advisory Board (CAB) serves as liaison to the Long Island business community. The CAB conducts a golf tournament and the annual fund campaign to raise unrestricted funds to support the DNALC. Chairman: Edward A. Chernoff,Motors & Armatures Inc. CSHL Trustee Liaison: Arthur M. Spiro Michael Aboff, Aboff’s Inc. Paul Amoruso, Oxford & Simpson Rocco S. Barrese, Dilworth & Barrese Thomas W. Bogue, Signature Bank Ed Blaskey, Commerce Bank Thomas J. Calabrese, Daniel Gale Real Estate Richard A. Catalano, KPMG, LLP James Chinitz, Population Diagnostics Dr. Robert Dickstein, Pall Corporation Candido E. Fuentes-Felix, M.D., F.A.C.S. David Garbus, Huntington Business Products Centre Lawrence Goodman, Curtis, Mallet-Prevost MaryJane Helenek, Luitpold Pharmeceuticals Arthur D. Herman, Herman Development Neil M. Kaufman, Davidoff, Malito & Hutcher John C. Kean III, Kean Development Corporation Dr. Norman Kelker, Enzo Life Sciences Cary Kravet, Kravet Fabric Laurie J. Landeau, V.M.D. Scott Livingston, Axiom Capital Management James E. Mattutat, Ingleside Investors John Passarelli, M.D. Patricia Petersen, Daniel Gale Sothebys Int’l Frank Posillico, Rosa Racanelli/Aireco Realty Corp. Christiaan B. Reynolds, Fimat, USA William D. Roche Charles R. Schueler,Cablevision Lee Shuett, Nikon Instruments KurtTimmel, Marsh, Inc. Jeffrey K. Tupper,U.S. Trust Company Robert Van Nostrand, OSI Pharmaceuticals Inc. Zock Zamaniyan, Eppendorf North America Teresa Kemp-Zielenski, United Way of L.I. Hans Zobel, Festo Corporation DOLAN DNA LEARNING CENTER EXECUTIVE DIRECTOR’S REPORT Preparing students and families to thrive in the gene age TECHNOLOGY ADMINISTRATION INSTRUCTION BIOMEDIA DEVELOPMENT Nancy Daidola Elna Carrasco John Connolly Adrian Arva Mary Lamont Jeanette Collette Eun-Sook Jeong Greg Chin Stacy Leotta David Gundaker Susan Lauter Cornel Ghiban David Micklos Natalia Hanson Chun-hua Yang Uwe Hilgert Karen Orzel Laura Johns Bruce Nash Carolyn Reid Erin McKechnie Amanda McBrien Danielle Sixsmith Lauren Weidler What does it mean to be human? The philosopher,theologian, sociologist, historian, scientist, and every man or woman on the street have different answers to this question. So, too, does the genome biolo- gist who determines and compares the complete genetic endowments of living entities. The human genome is composed of 25 kinds of chromosomes—22 autosomes, the sex chromo- somes X and Y,and the mitochondrial chromosome. Each chromosome is a package for a single, long, and unbroken strand of the molecule deoxyribonucleic acid (DNA). The exact sequence of A, T,C, and Gnucleotides that compose the DNA molecule running through each chromosome is unique to each person. Arrayed along the chromosomes are approximately 30,000 genes—stretches of DNA ranging from several hundred to several million nucleotides—that carrythe “genetic code” for making the pro- tein components of living cells. This code determines physiological and psychological “traits” that we inherit from our parents, thus setting the parameters of human life, health, and happiness. The human genome weighs in at about 3 billion nucleotides, and the genomes of any two people are99.9% identical. Expressed another way,DNA from two people will on average differ by about one nucleotide per 1000. This does not seem like much, but taken over the entire genome, it comes to 3 million differences. The same sort of reasoning applies to our closest living relative, the chimpanzee, whose genome is 99% similar to ours. This leaves room for about 30 million DNA differences between humans and chimps. These differences are caused by mutations that accumulate in DNA over time, so the number of mutations is roughly proportional to the amount of time since two groups have diverged from a com- mon ancestor. The majority of these DNA differences between humans and chimps are of little or no consequence. This is because only about 1.5% of the human DNA sequence actually carries the code for making proteins. Thus, by chance, most mutations are likely to occur outside of protein-coding regions. Even protein-coding regions can tolerate a good deal of mutation, for two reasons. First, the genetic code is redundant, such that a number of different nucleotide sequences can specify the iden- tical protein. Second, some physical changes in a protein do not actually alter how it functions. These gross comparisons can only tell so much. Better to compare individual genes. As one might expect, a number of genes have evolved (changed) rapidly since humans and chimps diverged from a common ancestor about 6 million years ago, including those involved in immunity,reproduction, smell, taste, skin, and hair. Especially intriguing are changes in a gene called FOXP2,which may have had a role in language development. Even so, gene-to-gene comparisons confirmthat the vast majority of human and chimp genes are functionally identical. This “conservation of function” extends throughout the evolutionary tree. Beyond 1 computer comparisons of gene and protein sequence, functional equivalence is convincingly shown by gene-transfer experiments, most commonly when a human gene is inserted into a living mouse to replace its mouse counterpart. In most cases, the human replacement gene functions admirably. This has led researchers to introduce human disease genes to create mouse models that mimic human dis- orders such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and breast cancer. There are even examples of human genes functioning perfectly well in yeast, the simplest form of advanced cell. The recent sequencing of the sea urchin genome traced elements of our genealogy even further back in evolutionary time. Surprisingly, the urchin has the most well-developed immune system yet encountered in an animal without a backbone. The urchin shares with us prototypes of genes for key growth factors and receptors that participate in immune and blood system development, including tumor necrosis factor, interleukins, and vascular endothelial growth factor. Going back further still, we share a basic set of genes—including those needed to extract energy from food—with the ancient archaebacteria that inhabit hot springs and deep-ocean vents. These gene comparisons illustrate that evolution has preserved gene “tool sets” that successfully carry out life processes—layering on new gene sets as organisms gained complexity. Genes Genome Size Organism (Nucleotides) Sequenced Year Archaebacterium (Methanococcus maripaludis) 1,880 1.7 million 2007 Bacterium (Escherichia coli) 4,400 4.6 million 1997 Baker’s Yeast (Saccaromyces cerevisiea) 6,190 12.1 million 1997 Fruit Fly (Drosophila melanogaster) ~14,800 180 million 2000 Roundworm(Caenorhabditis elegans) ~21,000 100 million 1998 Sea Urchin (Strongylocentrotus purpuratus) ~23,300 814 million 2006 House Mouse (Mus musculus) ~30,000 2.5 billion 2002 Human (Homo sapiens) ~30,000 3.2 billion 2003 As shown in the table, adding genes can add only so much complexity to an organism. Bacteria, sin- gle-celled organisms without an organized nucleus, get by with several thousand genes. Yeasts gain an organized nucleus with only about twice as many genes. The fruit fly gains a complicated body plan and external skeleton with only about twice again as many genes. Mammals gain an internal skeleton and temperatureregulation with only about twice the number of genes as a fruit fly. Here, the gene num- ber levels off, with essentially no difference in gene number between a mouse and a human. Clearly, humans share many genes with other organisms—especially other mammals. If this is so, how can we achieve “humanness” with essentially the same gene set as a mouse or a chimp? Much of the answer lies in “noncoding” DNA sequences that do not carry the genetic code for making pro- teins. Much of the noncoding DNA lies in between genes, separating them from one another on the chromosomes. This “intergenic” DNA contains key regulatory sequences—promoters and enhancers— that turn genes on and off in specific tissues and at specific times during development from embryo to adult. Altering the timing and interaction of thousands of genes can produce markedly different mor- Model organisms(left to right) E. coli,C. elegans,Drosophila,mouse, human cell, and Arabidopsis. 2 phological features. For example, the same set of regulatory genes defines the basic body plans of all animals with twofold (bilateral) symmetry. These “master” genes function in organisms as diverse as fruit fly to human, controlling the proper placement of body parts, from wings and antenna to arms and ears. In the mid-1970s, Rich Roberts, at Cold Spring Harbor Laboratory (CSHL), and Phil Sharp, at the Massachusetts Institute of Technology, discovered that genes themselves are interrupted by noncod- ing sequences. They shared the Nobel Prize for showing that noncoding sequences—termed “introns”—separate the genes of higher organisms into modular coding “exons.” The average human gene contains seven exons that can be joined together in different combinations to specify several dif- ferent proteins. This “differential splicing” further increases the functional complexity of the genome. Transposons, the so-called jumping genes discovered by CSHL Nobel laureate Barbara McClintock, are the largest component of noncoding DNA, equal to about half the total mass of the human genome! It could be worse, transposons account for an estimated 85% of the corn (maize) genome. Biologists are split about whether jumping genes serve some purpose in genome evolution or are just extremely effective genetic hitchhikers. Grand scheme or not, the most common human transposon, termed Alu, provides a sequence that is used in about 5% of differentially spliced exons. Introns and transposons account for most of the disparity between genome size and gene number as organisms increase in complexity. Thus, although the fruit fly genome is about 100 times as large as the archaebacterial genome, it contains only about eight times as many genes. About twice as many human genes occupy about 18 times as much space as the fruit fly genome. Comparing extremes, human genes occupy about 100 times the genome space of an equivalent number of archaebacterial genes! Thus, from a genomicist’s point of view, being human is a large endowment of genes shared with many organisms through evolutionary time, retasked by regulatory elements, and reshuffled through dif- ferential splicing. Gene sets for a basic bilateral body plan and mammalian way of life are further modi- fied by a relatively small set of genes peculiar to our kind. Inherited gene variations are further shuffled during the generation of parental sperm and egg. This shared heritage, attenuated by a unique set of mutations, comes together at the moment of conception to produce a unique individual—one with a brain that is capable of pondering why so much of his or her genome is given over to jumping genes. Dynamic Gene The more than 130 billion nucleotides of DNA sequence residing in Genbank and other databases now challenge biology students to come to grips with the complex genomes of higher organisms. The geneticist J.B.S. Haldane once famously said that the universe is not only stranger than we imagine, but may be stranger than we can imagine. He might as well have been talking about the human genome, chock full of noncoding introns and transposons, as well as a new class of RNA genes, that interact in unexpected and still largely unknown ways to regulate gene expression. Thus, in 2006, we continued our work with CSHL researchers to develop interfaces to DNA databases, which open a win- dow on the strange and wonderful world of genome science. The Dynamic GeneInternet site (www.dynamicgene.org) is the educational outreach component of Gramene, an online resource for analyzing and comparing genes from plants in the Gramineae, or grass, family. This group includes the cereal grains that feed most of the world’s people—rice, wheat, corn, barley, sorghum, millet, oats, and rye. The site is being developed in collaboration with CSHL genomicists Doreen Ware and Lincoln Stein, as well as three faculty producers: Debra Burhans (Canisius College, Buffalo, New York), Charlie Gutierrez (John H. Reagan High School, Austin, Texas), and Bob Wheeler (Pine Creek High School, Colorado Springs, Colorado). The site is designed to let students learn about plant genomes by using bioinformatics to analyze genes in the newly sequenced rice and maize genomes. Many of these genes have only been predict- ed by computers and have never been closely examined by human beings! The site’s name empha- sizes the gene both as a dynamic structurethat changes through evolutionarytime and as a dynamic concept that changes with our increasing knowledge of genome organization. The design forDynamic Generecalls the “streamlining movement” that influenced design during the middle of the 20thcentury with ideas borrowed from aviation and automobile design. 3 Animated tutorials in the first three sections—Meaning, Structure, and Evidence—illustrate (1) how DNA sequences encode biological information, (2) how bioinformatics uncovers sequence patterns that predict the structural components of genes, and (3) how computer-generated gene “models” are anno- tated with gene features and evidence from biological experiments. The Annotation section provides step-by-step instructions on how to analyze a gene model with Apollo,research software that was used to annotate the Drosophilagenome. Once students understand the basics of gene annotation, they go to the Projects section to download large DNA sequences from cereal chromosomes. They then pit their logic against the computer that predicted the gene models encountered and upload their new annotations to share with other researchers. Bringing Nobel-winning Science to Students With complete genome sequences accumulating at an accelerating rate, ahead lies the massive task of determining the physiological function of thousands of newly identified genes for which little is known beyond their sequences. The 2006 Nobel Prize in Physiology or Medicine recognized the discovery RNA interference (RNAi), a basic mechanism of gene regulation that also provides an important new tool for functional genome analysis. American scientists Andrew Fire and Craig Mello shared the Prize for showing that short, double-stranded RNA (dsRNA) molecules can down-regulate gene expression of a corresponding target gene. By deliberately introducing defined sequences of dsRNA into living organisms, biologists can observe the physiological consequences of “silencing” virtually any gene in Caenorhabditis elegans, as well as other plants and animals. MicroRNAs, which use part of the RNAi mechanism, have emerged as a powerful force in large-scale gene regulation and genome organiza- tion. CSHL researchers Greg Hannon, Leemor Joshua-Tor, and Scott Lowe have pioneered work on the mechanism of RNAi and its adaptation as a tool for genome exploration. Despite its power,RNAi is amazingly simple to perform in the roundworm C. elegans,animportant model system for eukaryotic gene function. Any gene of choice can be “silenced” merely by feeding wormsbacteria that express the correct dsRNA. In its simplest form, RNAi requires little more than the ability to grow bacteria and observe C. elegans traits with a dissecting microscope. The vast majority of high schools and colleges meet these requirements, making RNAi in C. elegans potentially more accessible than other molecular techniques for which specialized equipment is required, such as poly- merase chain reaction (PCR) and gel electrophoresis. For these reasons, we have devoted consider- able effort to developing the RNAi/C. eleganssystem as thevehicle to deliver functional genome analy- sis into high school and college classes. Considering the banner year for RNAi in Stockholm, our timing could not have been better as we completed our National Science Foundation project to develop an integrated experiment- and bioinfor- matics-based curriculum on RNAi in C. elegans.The curriculum begins with observation of mutant phe- notypes and basic worm“husbandry,” and then progresses to simple methods to induce RNAi and to use RNAi to rescue (compensate) a mutant phenotype. A more advanced experiment uses “single- wormPCR” to examine the mechanism of RNAi— comparing the DNA of worms with identical pheno- types induced by either RNAi or a gene mutation. The curriculum culminates with open-ended meth- ods that support student projects. Students can perform RNAi “from scratch” using bioinformatics to develop PCR primers for a target gene, then cloning the amplified product into an RNAi feeding vector, and finally observing the phenotype of treated worms. Students also have free access to the DNALC’s collection of RNAi feeding strains, which can be used to conduct a miniscreen to identify genes involved in a particular biological pathway. An online lab notebook, Silencing Genomes (www.silencinggenomes.org), combines lab methods with user-friendly features adapted from the DNALC’s popular text DNA Science,including flow charts, reagent recipes, and extensive instructor information. Supporting resources include photos and video of C. elegans mutants, as well as a simple checkout system to obtain any of 80 C. elegans mutants and Escherichia colifeeding strains. The Internet site also provides a launch pad for bioinformatics exer- cises that accompany each experiment. Students use online databases—including WormBase and Pubmed—to explorethe molecular genetics and physiological functions of the genes targeted by RNAi. 4 NCBI’s BLAST and the DNALC Sequence Server are used to explore the evolutionary relatedness of genes in worms and humans. The experiments wereinitially tested during a spring workshop of our Advisory Panel of 12 lead high school and college faculty from around the United States. Building on their feedback, the curriculum was then field-tested at summer workshops in Oklahoma City, San Francisco, and New York City, which were attended by 53 high school teachers, 6 junior college faculty, and 9 four-year college faculty. In addition, the RNAi curriculum was a major focus of the Amgen Leadership Symposiumand workshops conduct- ed for the Singapore Ministry of Education and the Novartis Exploratory Clinical Development Group. To get a quick picture of early classroom implementation, in December, we administered an online sur- vey for faculty who participated in testing summer workshops. The majority (71%) of respondents had already begun to integrate workshop content into their teaching, by using RNAi (51%) or C. elegans(41%) as examples while teaching about other topics or by teaching entire units of RNAi (37%) or C. elegans (16%). This teaching impacted 1781 students and 58 other teachers. More than a quarter (27%) had done one or morelabs—basic C. elegansmanipulation and mutant analysis (25% each), RNAi by feeding (16%), analyzing mutants by PCR (12%), and generating a targeting vector (4%). This lab instruction impacted 329 students and 17 teachers. The same proportion (27%) had used bioinformatics to analyze C. elegans genes or to compare worm to human genes, impacting 410 students and 19 teachers. Real-time Microscopy Exhibit The DNALC’s museum exhibits are tightly tied to experiments that students conduct in the teaching labs. For several years, an Applied Biosystems 307 DNA sequencer did double duty as an exhibit as it sequenced mitochondrial DNA samples isolated by students in the teaching labs and submitted from schools around the United States. As our volume increased to morethan 5000 student sequences per year, we shifted this work to a faster capillary machine at the CSHL Genome Center. In 2006, this space was taken over by a new Nikon Eclipse 80i microscope, with fluorescence and differential interference contrast (DIC) optics. A high-resolution digital camera output to a 46-inch LCD display allows us to dis- play striking, live images taken from the microscope. Real-time exhibits prepared each day give students a glimpse of the world as seen through this research-grade microscope. As a default, live mounts of C. elegansmutants, including the bizarre“bag of worms,” coordinate with an adjacent exhibit on key model systems used in biological research. At 5 Educator Lauren Weidler focuses in on C. eleganswith the Nikon fluorescence microscope and flat-panel display newly installed in the exhibit space. other times, mounts complement a variety of labs conducted by 5th to 12th grade students. Cells scraped from an instructor’s cheek, or stained chro- mosomes spreads, show the source of student DNA for human PCR. Live E. colior C. elegansexpressing green fluorescent protein (GFP) vividly illustrate the results of student’s own efforts to genetically engi- neer bacteria with the GFP gene. Mounts of plant and animal cells, as well as C. elegansmutants, rein- force student observations of differences in cell structure and variations in phenotype. DNA Sequencing Service The DNA Sequencing Service continued to offer students nationwide the opportunity to look at their own DNA sequence and to use it as the basis for understanding human diversity.Every human cell has a“second” genome, found in the cell’s energy-generating organelle, the mitochondrion. Mutations are common in partof the mitochondrial chromosome, largely due to exposureto oxygen-free radicals gen- erated as a by-product of energy production. Because of this mutational variability, the noncoding region of the mitochondrial chromosome is a mainstay in studies of human variation and evolution. The DNALC popularized methods to use mitochondrial mutation analysis in education, focusing on the same region of DNA featured in the National Geographic’s Genographic Project and the popular book The Seven Daughters of Eve.Using DNALC protocols or ready-to-use kits, students isolate a 440- nucleotide sequence of their mitochondrial genome, and then send their samples by overnight mail to the DNALC. At the DNALC, college interns Alina Duvall (Hofstra University) and Jennifer Aiello (Long Island University) perform dye terminator reactions that label student samples for DNA sequencing. The reactions arethen sent to the CSHL Sequencing Shared Resource Facility in Woodbury, where they are sequenced on an Applied Biosystems 3730xl Genetic Analyzer. The finished sequences are uploaded to a student DNA database at the DNALC’sBioServers Internet site (www.bioservers.org). Using bioinformatics tools at the Internet site, students can compare their own mitochondrial DNA with their classmates’ to see that people have inherited unique patterns of mutations. In comparing mitochondrial DNA samples from world populations, students can understand the evidence for the human lineage developing in Africa and recently migrating “out of Africa” to populate the rest of the world. Students can also compare ancient DNA samples from Neandertals and Otzi “the ice man” to understand their relationships to modernhumans. In 2006, we sequenced 6400 students’ DNA samples submitted from 31 states, Washington, D.C., and Canada. On average, results wereposted on the Internet site within 12 days of receipt. This unique educational system—DNA sequencing, student DNA database, and Internet bioinformatics tools—is provided free of charge to high school and college classes. This is made possible by the donation of sequencing reagents by Applied Biosystems of Foster City, California. Genes to Cognition Online We continued with key formative work on the new Internet site, Genes to Cognition(G2C)Online,which will explore the molecular basis of human thinking and disorders of thinking. During the first part of the year,we worked closely with advisorypanelist and education pioneer, Joe Novak, to develop methods to obtain detailed concept maps in three knowledge domains: cognitive disorders, approaches to sci- 6 ence, and systems-level biology. These concept maps form the backbone of the G2C Online“knowl- edge network,” which guides content development and defines how different content items are related toone another. Thirteen experts from neuroscience and education were interviewed: • Eric Kandel (Nobel laureate, Columbia University): Basic memory mechanisms • Steve Hyman (Harvard University Provost and Harvard University Medical School Professor of Neurobiology): Reward- and fear-based learning • Marilyn Albert (Johns Hopkins University): Alzheimer’s disease • Ray DePaulo and Kay Redfield Jamison (Johns Hopkins University): Bipolar disorder • Adam Kaplin (Johns Hopkins University): Depression • Alysa Doyle (Harvard University): Attention deficit and hyperactivity disorder • Daniel Weinberger (National Institutes of Health): Schizophrenia • Seth Grant (Wellcome Trust Sanger Institute): Genomic neuroscience • Joy Hirsch (Columbia University): Neuroimaging • Mary Colvard, Laura Maitland, and Caren Gough (Faculty Fellows): Biology and psychology education In conjunction with concept mapping, we developed an Internet-accessible editing system to meta-tag G2Ccontent. The system uses key words, scales, and classifications to define an item’s position in the knowledge network. A Yahoo! term extractor automatically identifies suggested keywords from any inputted text field. The item’s relevance is then rated according to 20 conceptual domains within biologi- cal systems, cognitive disorders, and approaches to science. The system also collects a number of basic data fields that we have developed as a collaborator in BiosciEdNet, a National Digital Science Library (NSDL) project headed by the American Association for the Advancement of Science. The NSDL meta- data scheme aligns with the other major projects and includes technical specifications, media type, edu- cational uses and context, end-user roles, knowledge taxons, creator information, life cycle, and rights. We chose autism as the topic for which to develop prototype content and interactive student activi- ties. Of note is an emotion-recognition game that highlights the difficulty many autistic people have in “reading” facial expressions. This engaging activity is framed within the context of current research on the neural and genetic basis of the disorder, including interviews with Trevor Robbins (Cambridge University), Ron McKay (University of Edinburgh), and Dan Geschwind (University of California, Los Angeles). Wealso Genes to Cognition (G2C) Online demonstration screen shots featuring autism. 7 capitalized on the project’s February Advisory Panel meeting at the Wellcome Trust Sanger Institute, videotaping interviews and lab demonstrations with collaborators on the G2Cresearch team. InJune, we conducted the first evaluation of the prototype site. High school biology and social sci- ence students reviewed two entirely different G2C Online designs and navigation systems. We were especially interested in their understanding of the purpose of the site and how to move from topic to topic. The student reactions and misperceptions prompted important changes that should improve how they interact with the site and integrate the “big” ideas we hope to get across. This study is the first of a number of keystone evaluations that will guide the development of G2C Online and, ultimately, demonstrate its usefulness in modern biology and psychology education. The project also gained insight from a high-level workshop, New Horizons in Internet Site Development,held October 22–25 at the CSHL Banbury Center. Co-chaired by Ed Rover, President of the Dana Foundation, and Marshall Smith, Director of Education at the Hewlett Foundation, the 2.5-day meeting drew together 30 experts and opinion leaders from diverse fields, including cognitive science, neuroscience, network theory, knowledge management, learning theory, and technology convergence. Acommon theme throughout the meeting was the growing ability of the Internet to connect people in real-time in “communities” of common interest. Among the presenters were Tim Tully (CSHL), Walter Baer (Annenberg Center for Communication), John Jungck (Beloit College), John Kruper (Cardean Learning Group), John Beisty (SAP America), and Katy Börner (Indiana University). A working paper on insights gained from the meeting was developed with the Center for Children and Technology (CCT), with whom we are collaborating to evaluate site development. New Horizons in Internet Site Development presenters Simon Buckingham (Open University) and John Kruper (Cardean Learning Group) network during session break. Conference organizer John Connolly and Katy Börner (Indiana University) discuss her talk on mapping science. RecordNumber of Real and Virtual Visitors in 2006 Annual visitation topped 40,000 in 2006. This included 29,657 students who conducted experiments with DNALC staff (on field trips to the DNALC or at their own schools) and 824 summer campers who spent a week at the DNALC—both record highs. The DNALC has been the beneficiary of a growing demand for science enrichment, precipitated by new teaching standards and the specter of the impending national science achievement test for 6thgraders in 2007. More than 60 school systems par- ticipated in middle school programs, and younger students comprised a majority of our clientele for academic year field trips and summer workshops. A typical middle school field trip includes a mix of hands-on labs (such as DNA extraction or bacterial transformation), guided tour of The Genes We Share exhibit, and virtual labs (such as The Mystery of Anastasia and Otzi: The Iceman Cometh). As basic genetics and biotechnology labs have moved increasingly to the middle schools, we have encouraged high school faculty to upgrade their instruction. Thus, more than half of high school field trips allowed students to look at their own DNA and to understand how DNA differences (polymorphisms) are used to understand human evolution. 8