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Earthwatch high schoolers help decipher human genome

Appropriately dressed in a black T-shirt emblazoned with a colorful representation of a DNA molecule, Lane Conn explains how to decode a strand of DNA.

His lab team, armed with notebooks and binders, crowds around a table overflowing with equipment. Conn, education director at Stanford's Human Genome Center, gestures to an upright rectangular box holding what looks like a slab of clear gelatin surrounded by wires.

"So now we're separating DNA that we synthesized yesterday by size. Each differs by only one nucleotide," Conn tells the students who watch closely, occasionally scribbling down notes.

The six students from high schools around the country won scholarships from the Student Challenge Awards Program to do a two-week project sequencing DNA at the Genome Center.

The program was developed by Earthwatch, an organization that supports scientific field research worldwide. It is funded by the Durfee Foundation, which awards grants for study in the areas of arts and culture, education, history and community development.

The students' project puts them in a class with hundreds of scientists around the world trying to decipher human DNA, the molecule that provides the instructions for life. Imagine DNA as a spiral staircase, with each step representing a single unit of the genetic code. The human genome has 3 billion of these units, called base pairs, of which the students will be sequencing about 1,000.

"These students are doing original research that no one has ever done before," Conn says. "They are the first ones in the world to analyze this kilobase of sequence."

The DNA sample was provided by Mary-Claire King's lab at the University of Washington, which linked this area of DNA to a form of hereditary deafness in a Costa Rican family, Conn says. The sequence provided by the students will be sent back to King's lab and eventually become part of a searchable database. The students will be able to follow their DNA on the Internet years after the project is done as other scientists work to understand its function.

So how do you teach a group of high school kids with fairly limited science backgrounds to do cutting-edge genetics research? "Immersion is the key," Conn says. "Everything the students do is related to molecular biology and genetics. We don't let them think about anything else."

But it's not easy. "The hardest thing for me was learning all the words," says Julia Bonack of Mayville, Wisc. "We don't do stuff like this in my high school. I like biology, but they don't offer much."

The gels are heating up in preparation for loading, and Conn briefly explains what the group is about to do. The DNA was previously broken up into pieces, each differing in length by only one base pair. The students will inject small amounts of DNA into the tops of lanes running down the length of the gel.

An electric current running through the gel pulls the DNA fragments, which are negatively charged, through the gel and toward the positive electrode at the bottom of the box.

"There are millions of molecules of DNA in there," Conn tells the group. "What allows this to work is that different sized molecules move at different speeds through the gel." He likens it to the opening and closing of a fast elevator door; small fragments move through faster and get to the bottom first.

After about two and a half hours, the DNA is spread out down the gel enough for the students to make a visual image of where the strands of DNA have stopped along their paths.

To do this, they lay the gel flat and cover it with a nylon membrane. They lay eight heavy volumes of the science journal Cell on the nylon to help it soak up the DNA-filled moisture from the gel. The students then expose the nylon to ultraviolet light in a machine called a cross-linking chamber, which bonds the DNA in position on the membrane.

"To read the sequence," Conn says, "all you have to do is start at the bottom and read up."

At least, that's how it's supposed to work.

Two days later, the students are back in the lab, doing the whole thing over again.

Asked what happened to the last preparations, Maria Reeves, the students' mentor, starts to say that everything got messed up and then grins. "Now we call them 'learning experiences,'" she says, and the students laugh.

The gels that the students produced in their last effort were unreadable, Reeves says; the DNA mixtures leaked from one lane of the gel into other lanes, making it impossible to read the order of the nucleotides.

Conn reminds the students, who are redoing the gels, that experiments must often be rethought and redone many times before they work properly.

In a nearby conference room, Andrea Burnside of New York City, Yvonne Lai of Holmdel, N.J., and Bonack stare intently at long sheets of paper a few inches wide that hold the information from the previously done photographs. The code from the DNA should be clearly expressed in little dashes, each dash representing a nucleotide, half of a base pair.

The students list the order of the nucleotides as best they can, but not all the dashes are clear. They blend into each other at points, and sometimes they are so faint they are unreadable.

"This is a mess," Lai mutters. "Our data ran together, and some just didn't show up." Lai squints at the paper, trying to determine if a faint mark represents a nucleotide or just a streak.

"While loading the gel, we poked holes in it where they shouldn't have been," Burnside explains, "We're new at this."

"They have machines to do [the sequencing] now," Lai adds. "They wanted us to do it manually to make us appreciate the technology." She grins ruefully, glancing at her half-filled sheet of sequence. "It's working," she says.

Ethics and genetic research

The genome center project exposes the students to more than the science of DNA sequencing. They also learn about the ethical issues involved in genetics research. Understanding the ethics is important because in the future, the students as citizens will have a say in how this technology is used, Reeves says. "[They will] decide whether the benefits of these technologies outweigh the consequences."

Over a Friday afternoon brown-bag lunch, David Cox, co-director of the genome center and member of President Clinton's National Bioethics Advisory Committee, discusses the ethics questions with the students.

Knowing the sequence of the genome is only the beginning, Cox says. Deciphering the genome eventually could lead to more treatment options for people with genetic diseases, but currently, the ability to diagnose far outweighs the ability to treat. "People like fortune-telling, especially if it gives them options," Cox adds.

Cox talks about a late-night call he received from the White House telling him to come to Washington, D.C., for an emergency meeting after Dolly the sheep was cloned. "I never thought there would be an emergency meeting called for a bioethics committee," he says with a laugh.

The committee was given 90 days to come up with suggestions for the president on how to proceed with the issue of human cloning research. "We recommended a moratorium on the process, and we also recommended a federal law against [attempting to create a child through cloning]," says Cox.

"These issues are going on now," Cox tells the students while he emphasizes the importance of public discussion about ethics and genetics. Acting on advice from the bioethics committee, President Clinton recently endorsed legislation to prevent health insurance companies from denying healthy people coverage based on genetic tests.

Cox also warns against overestimating the predictive power of genetic tests: "This technology is only as good as the common sense that you use it with."

Back in the lab, the students explain their project to two visitors from the sponsoring Durfee Foundation.

The genome center team is the only Earthwatch group working solely in a lab this year rather than doing field research. It's a source of pride for the group. "We're not out chasing squirrels or whatever," Barbara Hidalgo-Sotelo of Austin, Texas, says.

Claire Peeps, the foundation's director, says that the genome center was chosen to challenge the students. "They are doing real research that is useful," says Peeps, who has come to watch the students at work. "It's not just a training experience."

But David Szyszka of Bearsville, N.Y., who is over at the hot water bath preparing the DNA, comes back with some bad news. A microcentrifuge tube with a DNA mixture was open, and its contents just spilled out into the water bath. "We have to redo it?" Hidalgo-Sotelo asks in disbelief. "We just had another learning experience," Reeves tells Conn as he walks in the room.


By Libusha Kelly

Libusha Kelly is a science writing intern at the Stanford News Service.