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Mario Capecchi, Distinguished Professor, Eccles Institute of Human Genetics.
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Mario Capecchi in his laboratory.
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Mario Capecchi and members of his lab.
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Mario Capecchi and his daughter Misha.
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Mario Capecchi with his wife, Laurie Fraser, and daughter Misha.
Audio Glossary
Southern blot, Knockout, Mouse model, Polymerase chain reaction (PCR), PrimerVideo Interviews
Dr. Brian Sauer is the head of the developmental biology research program at Oklahoma Medical Research Foundation.
Clip 1 (1:03)
The simplicity of the cre/lox system.
Clip 2 (0:48)
How the cre/lox system works.
Clip 3 (1:04)
How to cut out a gene and why would anyone want to.
Clip 4 (1:25)
How the idea of the cre/lox system come about.
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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.
MARIO RENATO CAPECCHI (1937-)
In 1980, Mario Capecchi faced an uncertain future. Reviewers deemed the research proposal he sent to NIH "not worthy of pursuit," so Capecchi gambled and diverted money from other projects into the new research. If the gamble didn't pay off, Capecchi risked losing all his research funding, a death sentence for researchers in today's publish-or-perish universities. But for a man who spent five years as a homeless orphan on the streets of war-torn Italy, the risk probably seemed insignificant. During the first four years of his life, Capecchi lived with his mother, Lucy Dodd-Ramberg, a poet. Lucy joined a group of artists opposed to fascism in northern Italy, where she met Mario's father, an officer in the Italian air force. Capecchi says they had a passionate love affair, but she wisely refused to marry him. When World War II started, Mario's mother, along with the other Bohemian artists, was arrested by the Gestapo and sent to Dachau. Lucy anticipated the arrest and arranged for Mario to live with friends with the money she received from selling all her possessions. After a year, however, the money ran out - or was stolen by Mario's father - and the five-year-old was left to fend for himself. Mario headed south and joined gangs of other homeless orphans, stealing food from open-air markets and sleeping in bombed-out buildings. The police captured him again and again and sent him to orphanages and hospitals, but life there was worse. In the hospital, a cup of coffee and a piece of bread once a day were used to treat his malnutrition, and Mario spent the days lying naked on a stripped bed in a feverish delirium. After the war, Capecchi's mother was released from prison and searched Italy for a year before finding Mario in a hospital in Reggio Emelia, a city near Bologna. The woman didn't look like the mother he remembered, but she promised to take him from the hospital, so he traveled with her to his uncle's Quaker commune outside Philadelphia in the United States. Edward Ramberg and his wife, Sarah, struggled to tame Mario, now 9, when it became clear that Lucy was too psychologically scarred from the war to care for him. Mario entered third grade at the local public school without knowing English and spent most of his time beating up his classmates. By high school, he had been socialized, partly through his participation in sports. Capecchi thinks playing on the school's football, baseball, soccer, and wrestling teams taught him lessons in human psychology that he eventually transferred to later relationships. In college at Antioch, Capecchi began studying for a political science degree to combine his esteem for science with his sense of social responsibility. But he found little science in politics and abandoned it for physics and chemistry. Before he graduated in 1961, though, he knew he would make another switch to molecular biology in graduate school. The field was so new that anything was possible and you could ask any question. Capecchi's graduate advisor at Harvard, James Watson, steered Mario away from small questions that were only likely to produce small answers. By 1967, Capecchi had his doctorate and, in 1968, joined the biochemistry faculty at Harvard Medical School. Even though there were thousands of researchers and potential collaborators in the Boston area, Capecchi felt he needed more isolation to freely pursue the big questions in his head. In 1973, he moved to the University of Utah in Salt Lake City where he had 20 colleagues in a department that covered everything from evolution to molecular biology. The professional gamble Capecchi took with his research funding in 1980 paid off, and he was on his way to harnessing the machinery of mammalian cells to precisely mutate any gene he wished. The technique not only helps researchers generate mice with human diseases for study, but it may be used in future gene therapies to correct disease-causing genes. When he reapplied to NIH in 1984, the reviewers admitted their goof: "We are glad that you didn't follow our advice." Mario Capecchi is currently a professor of Human Genetics at the University of Utah and lives with his wife and daughter in a remote house in the mountains near Salt Lake City. In 1996, he received the Kyoto Prize honoring his lifetime achievement in the betterment of humanity. BRIAN SAUER (1949-)
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 runs the Developmental Biology Research Program and the mouse knock-out facility. 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. |
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LinksEmbryo ImagesThis site has scanning electron micrographs of developing mammalian embryos, mostly mice though there are human embryo pictures. Normal and abnormal development are featured in tutorials based on body parts. Of Mice and MenFrom the Howard Hughes Medical Institute, an article on the how gene targetting works in mice. Holliday StructureA brief description with an animated gif of how strand exchange works between two pieces of DNA. Bibliography
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