Concept 41 DNA is only the beginning for understanding the human genome.

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Mario Capecchi developed a technique to target and mutate genes in mice using homologous recombination. Brian Sauer adapted the cre/lox recombinase system from phage for mammalian gene knock outs.

Brian Sauer may be one of the few scientists whose interest in science nearly got him arrested. Sauer (pronounced 'sour') set up his telescope in a dark lot in a nearly deserted housing development to watch Halley's comet. The few houses scattered about looked empty, but one little old lady spotted him and called the state police. Sauer avoided a night in jail after offering the officer a close-up view of the comet.

Growing up on his family's dairy farm north of Madison, Wisconsin, Sauer's first scientific interest was astronomy. He constructed his first telescope from a cardboard tube and fitted it with four lenses. "I grew up in the country, and the sky was always dark," he said. "In school, I told people I was going to be an astrophysicist."

For his first five years of school, Sauer attended a one-room schoolhouse with children in grades one through eight. Around December, he remembers, "there was always a school play and there would be no more classes because the teacher was too busy teaching everyone their parts." To kill time between rehearsals, Sauer played poker with the older students.

Along with the telescope, Sauer also built a short-wave radio and listened to Canadian stations. "But when you're living in Wisconsin, that's not much of a challenge," he confessed. Upping his range, he also managed to pull in European stations and listened to the shows they beamed to the U.S. in English. The experience led him to write a school essay on the propaganda the Nazis broadcasted to the Allied troops during World War II.

During recess at school, Sauer would join the other boys for a game of baseball. (Before astrophysics, Sauer wanted to be a Major League pitcher and he still thinks ex-Milwaukee Brave Warren Spahn was one of the best ever). Their baseball field bordered a swift-running creek, so left-field foul balls would land in the water. Since they only had one ball to play with, Sauer and his teammates would yell "Creek ball!," and everyone had to run to the creek to fish the ball out. "We had to get it before it flowed under the overpass," Sauer says, "because if it flowed past that, it was gone forever."

After high school, Sauer began studying physics at the University of Wisconsin in 1967 but found it tedious and switched to mathematics. One day during his senior year while he was working on a math problem on the big blackboard in his living room, his roommate came in and started sketching the structure of DNA. Intrigued by the molecule, Sauer went to work in a lab in Madison after graduating with a mathematics degree.

"I was a mathematician who was interested in doing some biology, and the most interesting thing about biology, according to my view, was genetics," Sauer recalls. With that in mind, Sauer started graduate school at the University of California, Berkeley in 1973. He worked on the P2 phage, what he calls the "other" phage, since most virologists worked on lambda at the time. When Sauer traveled to conferences to give talks, only ten or so hungover scientists would hear his presentation, because the session on the "other" phage was always scheduled for Sunday morning.

Following a post-doc at Stanford University and a position at the National Cancer Institute, Sauer followed his NCI boss to DuPont in 1984. His colleagues had worked out the biochemistry of the cre/lox recombinase system in the P1 phage, and because the biochemistry was simple, he thought it would also work in eukaryotic cells. Sauer picked the brains of the yeast experts next door and inserted the system into the fungus, expecting sluggish recombination. Instead, "it turned out that the cre worked very efficiently," Sauer says. After the system also worked in mouse cells, he realized "now we could do things [in mammalian cells] that had been done in Drosophila 50 years before."

In 1998, Sauer moved to the Oklahoma Medical Research Foundation where he ran the Developmental Biology Research Program and the mouse knock-out facility. He was then Director of Transgenic Technologies at the Stowers Institute, before moving into genetic engineering consultancy. His research tries to untangle the mechanism of DNA recombination with the ultimate goal of applying this knowledge to more precise redesign of the mouse genome.