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 Dr. Jim Bonacum, Scientific Director of the Genomic Lab, in the exhibition, "The Genomic Revolution." The rainbow array behind him graphically represents the enormous volume of information in the human genome.
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It wasn't until Jim Bonacum went back to finish his degree in biology and taught undergraduate courses that he realized how much he liked teaching. And it wasn't until he started doing molecular work at the American Museum of Natural History one summer that he realized "how much we can learn from DNA sequence data." Jim's two passions came together in the spring of 2001, when the Museum's exhibition on the genome, "The Genomic Revolution," opened to the public. The exhibit contains a fully functional genetics laboratory. Jim's job in the lab is to explain basic molecular biology techniques to visiting school groups. "I like the idea of exploding the myth that genetics is very hard, complicated stuff," says Jim. "Hopefully I have been able to communicate my enthusiasm to the students."
The exhibit covers everything from what genes are and what they do, to the ethical implications of cloning or genetically modifying organisms. The exhibit's purpose is broad: to explain the impact of recent advances in genetics on "modern science and technology, natural history, biodiversity, and our everyday lives," as the Museum brochure describes it. Putting the significance of the recent sequencing of the human genome in a historical perspective, Jim notes that almost all of the major technical innovations of the 20th century—such as electric lights, radio, and the automobile—were in place in the early 1900s, and that most of the technological advances of the last 100 years have involved merely refining them. "The first great technical innovation of the new millennium is the sequencing of the human genome. But we have only the faintest inkling of what the genome actually means, and where this new knowledge is going to take us—only that it will bring about astonishing changes for all human beings," he predicts, as do many of his scientific colleagues.
The glassed-in genetics lab in the exhibition holds up to 36 people, and contains all the equipment necessary to extract, isolate, visualize, and sequence DNA. The lab is a collaboration between the Museum and the DNA Learning Center in Cold Spring Harbor, New York, which is associated with the Cold Spring Harbor Laboratory, one of the world's premier genetic research facilities. The collaborators' shared mission is to explain to middle and high school students what doing molecular biology really means, but the Exhibition's Learning Lab programming also takes the general public into consideration. Because visitors come in with different backgrounds and levels of knowledge about genetics, Jim and his assistant, Otis Robinson, briefly cover key concepts—"such as the double-helix structure of DNA, the fact that genes are used to make proteins, and some of the mechanisms of transcription and translation"—in an introductory presentation.
The first step in an hour-and-a-half visit to the lab is obtaining DNA samples. Visitors are asked to swish a saline solution around in their mouths and then spit it into cups. "The saline in the cup contains some of the cells that line the inside of the cheek. We then heat the cells to break them open, and mix them with a resin that binds to the proteins found within the cell. This separates the DNA from the rest of the cellular material," Jim explains. "Then, once the DNA is isolated, we perform several PCR experiments." Polymerase chain reaction, or PCR, enables biologists to isolate a specific fragment of the genome and to make multiple copies of it so that it can be studied and manipulated. "The kids assemble the PCR reactions themselves," he continues.
Dr. Jim Bonacum and Otis Robinson, Genomic Lab Assistant, working in the lab.
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Jim and Otis then use an agarose gel to render the results visible. "One experiment illustrates variation at the level of the chromosome. Some people have a particular insert in a chromosome at this position, and some people don't," Jim explains. "The purpose of this experiment is to give an idea of the variation within humans. In another experiment we amplify segments of the Cytochrome B gene, which is frequently used to understand evolutionary relationships among mammals. Students can then compare their own Cytochrome B gene sequence with the homologous sequence of various other mammals. This experiment is similar to what we do here at the Museum, where we use molecular data to conduct research in evolutionary biology."
During the DNA extraction and amplification process, which takes the machines about 90 minutes to complete, Jim and Otis explain how the PCR and DNA sequencing processes work, and send their visitors out to see the rest of the exhibit. When they return, participants receive a picture of the gel in which their amplified DNA is visualized as a bright band. Amplification is only the first step in the sequencing process, but it is all that a typical Museum visit allows time for. "Everybody, even the experienced scientists I work with, gets a kick out of seeing his or her own DNA sequence," Jim comments with a smile. "The experience helps bring the whole human genome project home. When I first learned these techniques in a class I took as an undergraduate, I had an abstract understanding of the process, but they weren't real until I actually did them in a lab myself." At the end of the session, everyone also takes his or her DNA sample home.
Before leaving the Learning Lab, students receive instructions on how to get to the AMNH lab's Web site, where they can compare their Cytochrome B sequence to that of other mammal species, as mentioned above. The Web site also contains a cladogram—a diagram that shows the evolutionary relationships between mammals. "They're surprised by how similar their DNA is to that of various mammals, and by the fact that certain mammals are less different from us than others," says Jim.
"We do the actual sequencing after the students leave, because it's very similar to assembling a PCR reaction, which they've already done, and it takes more time," explains Jim. "We clean the PCR products, perform the actual sequencing reactions, and then run them on an automated DNA sequencer, which takes about seven hours. Within a couple of days we post the data on the Web site for people to see." In order to maintain privacy, each DNA sequence is identified only by a randomized number, which the students take away with them.
On view in the exhibition, these bottles containing DNA smaples from a wide range of species, from house pets to endangered animals. Researchers at the AMNH have used these specimens to identify and classify species of plants and animals.
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Unfortunately, replicating this experience in the classroom is well beyond the resources of most schools. "If you were really determined, you could do the PCR amplification process by using water baths of different temperatures, the way the process was originally done, but it's tremendously labor-intensive," says Jim. "And you need a machine to do the DNA sequencing." The Museum is hoping to develop a mobile version of the lab and send it out into the New York region. Teachers like Jim will train other teachers to use the equipment, collect the amplified PCR fragments, and return it to the Museum to be sequenced. (See the In the Community feature of this issue for suggestions about local resources to draw upon for similar experiences.)
A visit to the lab will be most people's first up-close and personal exposure to the world of genetics. What Jim is really looking forward to is "a person walking out saying, 'I didn't think I could do this, I thought I wouldn't understand it, and wow, it was great! I really had a good time.'" Jim also confesses to a fantasy that one of his visitors will win the Nobel Prize in 2040, "and stand up and say, 'It all started when I went through the genetics lab at the American Museum of Natural History.' That would be a bigger thrill than winning it myself!"
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