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Animations & Movies:

DNA Replication

Sterile Lab Technique

Dan Branton on DNA Sequencing

Writer-director Cheryl Vaughan sits at the lab bench, fine tuning the script and beginning to sweat from the hot bright light that Leigh Stimolo is focusing on her. Vaughan is standing in for Ridgely Fisk Green, the on-camera talent who will arrive in a few minutes  and be dusted with makeup to look fresh for the actual shoot. Lansing Wagner, who’ll be monitoring the sound recording, is checking audio levels and positioning the boom mic. Steve Kierstead is training a tripod-mounted Canon XL-1S digital camera on the wilting Vaughan, adjusting the color balance and aperture.

Shooting on location is always risky, and everyone knows it’s going to be a long, grueling day in the basement of the Harvard Biological Laboratories. Construction noise from outside, plus the rumblings of the old building’s innards, ruins the soundtrack on otherwise good takes and forces the crew to shoot the same scene over and over. Patience, says director Vaughan, is essential.

Although this busy team could pass for an indie film crew, every one of them has a day job in Harvard’s Department of Molecular and Cellular Biology (MCB). And instead of working on an avant-garde feature for the Sundance Film Festival, they are making a short film that explains how the immune system makes antibodies and how these are used in laboratory research. A mix of animation and digital video will dramatize basic concepts and bench procedures not just for Harvard students but also for thousands elsewhere. In about two years, an archive of such films—all created by MCB faculty and staff—will be available at no charge to any student or teacher with Internet access.

These short films are the fruits of the Howard Hughes Medical Institute (HHMI)/Provost Media Project, which is MCB’s latest and largest movie venture but certainly not its first. Since the mid-1990s, individual professors have been working with media-savvy students and freelance animators to turn challenging concepts into cartoons they use for their own courses. Their piecemeal efforts got a boost in 2000–2001, when development of multimedia teaching tools was tied to a sweeping overhaul of the introductory course series, BioSci 50, 52, 54, and 56.

“Teaching is more than deciding what to teach and designing individual courses,” says Robert Lue, director of undergraduate education for MCB and current course head of BioSci 54 (Introductory Cell Biology). “It’s also about creating new and innovative materials that can be used not just here at Harvard, but also as a contribution elsewhere.”

Lue says MCB’s mission has four main thrusts: faculty research, undergraduate teaching, science outreach, and multimedia. Revelations in the laboratory have made it passé to reduce complex biological phenomena to a string of genetic code, so scientists now talk about structures that interact, change, and move. And this is why movies—and biologists who know how to make them—are becoming hotter than Hobbits.

Animating biology

“The initiative came from undergraduates,” Richard Losick says of the two-dimensional animations that are an integral part of BioSci 52 (Introductory Molecular Biology). Losick is a Harvard College Professor and Maria Moors Cabot Professor of Biology. About seven years ago, a gung-ho group of students offered to try to render all the course’s major concepts as animations, and Losick said yes. They began working on a set of two-dimensional FLASH animations, and although some of the early ones were “pretty primitive,” says Losick, the most artful and effective ones were created by students “as good as any professional.” Over the years, many of these student animators have been applied sciences concentrators preparing for careers in medicine or biomedical engineering.

Animations are especially important now that structural tools like X-ray crystallography make it possible to visualize the replisome, ribosome, and other macromolecular machines inside cells. “When something is complicated and involves dynamic processes, the best way to teach it is to pull out every trick in the book,” Losick says with a grin. His pedagogical repertoire includes lectures, textbooks, Power Point slides, physical models, and cartoons that move more fluidly than The Simpsons (but lack the depth of Shrek).

In 2002, Losick was one of 20 faculty members at research universities named HHMI Professors, an honor that brings $1 million to invest in improving undergraduate teaching. Losick is using part of the grant to bring the expertise of Matthew Bowen, a Michigan-based animator originally trained as a biologist, to bear on teaching materials for BioSci 52. “Every year I update the animations and get rid of the old ones and add new, improved ones,” Losick says. Today, students see 23 zippy, custom-made animations during the semester.

Losick’s storytelling philosophy is to start simple, often with the basic chemistry of a process, and then layer on complexities “so the student gets a progressively more sophisticated understanding of what’s going on.” One of his current favorites is an animated depiction of DNA replication: it starts with a double strand of DNA; adds helicases, polymerases, and other proteins; and ultimately shows the whole machine in action.

Animations are by necessity an oversimplification of what really happens inside cells, Losick observes, because “molecular biology is not a cartoon.” But they help him summarize complicated lectures in the classroom, and students who watch them again on the course website often find that “animations help them understand things faster and more efficiently,” Losick says.

Watch your hair

When MCB faculty members were revamping the introductory courses, they decided that the laboratory experience would be better if students spent more time doing hands-on experiments and less time sitting back and watching cells divide. Cheryl Vaughan came on board as preceptor for BioSci 54 in 2001, just as this effort was being launched. In collaboration with course directors Robert Lue and Raymond Erikson (John F. Drum American Cancer Society Professor of Cellular and Developmental Biology), she planned a multistep experiment that at one point required students to use immunofluorescence to verify that they had separated one cell type from a heterogeneous mixture. To do this, they would have to use Harvard’s expensive fluorescence microscopes.

“This idea behind the first video was that we didn’t want them touching those microscopes without knowing how to handle them,” Vaughan recalls. Lue secured a grant from the Provost’s Fund for Innovation in Technology, and they soon generated several short videos—each lasting less than 10 minutes—explaining how to use various microscopes, follow sterile procedures, and operate common lab equipment.

Cheryl Vaughan and Leigh Stimolo
Vaughan is the person on screen for these videos, and a potentially dramatic moment occurs during her introduction to the Bunsen burner, when she demonstrates the importance of keeping long hair away from the flame.

Similar “prelab” videos are also an integral part of Losick’s introductory molecular biology course. BioSci 52 preceptor A. Thomas Torello says he and Losick choose topics that are “really important for students to understand, but you don’t want to take lecture time to explain.” For example, some students are adept with a micropipette when they enroll, while others have never even held one. Teaching fellows differ in explanatory skills and patience, and in addition to saving class time, the prelab video “really levels the playing field so that every student has the same introduction,” Torello says.

Students are responsible for watching the prelab video on their own, and to make sure that they’ve actually done so, teaching fellows administer a quiz that students must pass before touching anything in the lab. And if they haven’t mastered the material, the video is ready to run on a nearby computer.

Dreamworks on the Charles?

Over the past three years, MCB has pulled together what amounts to a virtual multimedia production studio. A key player is Leigh Stimolo, who before joining MCB in 2001 had worked on independent films, produced and directed TV commercials, and founded her own video production and web design company. As a multimedia professional, she’s as novel in academia as computer experts were 30 years ago.

When Stimolo came on board, her first task was to shop wisely for lights, cameras, sound equipment, backdrops, editing software, and the other necessities of video production. Thus equipped, MCB was able to win HHMI support for what is officially called the Biological Sciences Multimedia Project. This grant underwrites video shoots such as the one described earlier, where Stimolo plays a key role.

The finished product will combine video segments, dispensing practical advice about a key lab technique or data analysis method, with animations that zoom in to show exactly how it works. These are packaged with an introduction and conclusion, delivered by project director Robert Lue, and include a stylishly produced interview with a Harvard faculty member that illustrates the value of the technique.

Robert Lue
While these multimedia teaching modules are the most obvious “deliverable” for the four-year HHMI grant, the act of producing them in-house may have an impact that outlasts the initial funding. “We’re trying to set up an infrastructure and a community of individuals who work together in a consistent, sustained way to create these materials,” Lue says. At the heart of this effort are the preceptors for the four introductory BioSci courses. Tutored by Stimolo, these professors of tomorrow have learned to storyboard, write scripts, direct video shoots, work with animators, and understand postproduction work.
With this in mind, course directors are recruiting preceptors who care about media as well as science education. “We’re not just people who write problem sets or work with teaching fellows and students, but people who think about biology education for all students, not just those who come to Harvard,” says Cheryl Vaughan, preceptor for BioSci 54. She and her counterparts in the other three courses are responsible for completing one multimedia production each year, sharing equipment, video crew, and animators.

MCB staff members have also joined the department’s multimedia team. Camera operator Steve Keirstead and audio technician Lansing Wagner both work in MCB teaching labs, setting up experiments and making sure the labs run as they should. Students are also integral to the project, helping research content and participating in video shoots as on-camera talent or production assistants. About 15 undergraduates, graduate students, and postdocs have participated so far—including Ridgely Fisk Green, a BioSci 54 teaching fellow who starred in Vaughan’s “Production of Antibodies” video. (Positions paying $12/hour for undergraduates and $25/hour for graduate students and postdocs are available. For more information, contact stimolo@fas.harvard.edu.)

What the multimedia project lacks is a permanent production studio where equipment can remain in place instead of being schlepped from one classroom to the next, and where soundproofing will keep dinging elevators and grinding dishwashers from spoiling otherwise good takes. Lue hopes that Harvard will eventually have a multimedia production facility that MCB and other Faculty of Arts and Sciences departments share, possibly as part of a new Institute for Innovative Computing in Allston.

In the meantime, the hub of MCB’s multimedia activity is http://multimedia.mcb.harvard.edu/, the website that serves as a kind of digital water cooler where preceptors (wearing their writer–director hats) and crew members meet to exchange progress notes, reserve equipment, post their rough cuts, pay their student assistants, and otherwise do what needs to be done.

A picture is worth…

The ultimate question, of course, is whether videos and cartoons actually help undergraduates learn the increasingly complicated “basics” of modern biology. Although there is scant research on this topic, Lue’s BioSci 54 team did a small study in 2003 and 2004.

In the first phase, two groups of 65 students were allotted two hours to study materials explaining how proteins are transported from the cytoplasm into the nucleus. One group was provided with a three-minute animation and written notes for a script explaining the action; the other was given relevant portions of a leading cell biology textbook. When they were tested at the end of the study period, students who used the animations outperformed the textbook group on factual questions (92% versus 78%) and on questions requiring data interpretation or synthesis (88% versus 61%).

In phase 2, the setup was the same but the study time was cut to one hour. While scores fell dramatically for the textbook group, they remained surprisingly stable for the students using the animation and script.

To professors like Lue and Richard Losick, who long ago incorporated moving pictures into the traditional lecture-and-lab format, this finding comes as no surprise. They say it takes a long time to explain, standing at the front of a giant lecture hall, what an animation can present in a few minutes and students raised on computer games seem to grasp in an instant. 

There’s an old saying that “One picture is worth a thousand words.” For Harvard biology students, it may be that a three-minute animation is worth an extra hour of study time.