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Life's Little Secrets: OU scientist in demand for genomic knowledge

2001-03-20
By Chip Minty
Staff Writer

It was Feb. 28, 1953, when Francis Crick and James Watson walked into a smoky pub in Cambridge, England, and announced they had found the secret of life.

It also became a defining moment in Bruce Roe's life.

The George Lynn Cross research professor of biochemistry at the University of Oklahoma was a schoolboy growing up in Long Island, N.Y., at the time. But the historic discovery has guided his career like a beacon.

Roe was a graduate student when he read Watson and Crick's paper. He was intrigued by their explanation of the DNA structure and how it forms a double helix that can make copies of itself. And he was inspired by their conclusion that DNA really does carry life's hereditary information. More than 30 years later, Roe still cites their research paper as a milestone for science and for him.

The secret they found 48 years ago may turn out to hold the answer to any number of questions in medicine, evolution and disease for people as well as animals and plants.

Some of those answers are beginning to fall out of vast combinations of genetic code unraveled over the past decade by the Human Genome Project, funded by the National Institutes of Health.

Roe's Advanced Center for Genome Technology was among an international consortium of 20 laboratories on the project to map each human gene and to completely sequence human DNA. The group published its first paper on its findings in the journal Nature last month.

The 3 billion characters that comprise the human genome have been compared to a blueprint for human life. Understanding the information contained in the genome will lay the foundation for medicine in the next century.

Unlocking the human genome, defined as all the genetic material contained in the body, is like putting together the dictionary of life.

"We're getting close to having all the words," Roe said. "From there, we have to determine the meaning of those words."

While Roe expected the project to be successful, he's surprised at the speed of the accomplishment, attributing much of the credit to fast-developing DNA-sequencing technology.

He compares DNA to a long strand made up of 3 billion beads. Each bead represents one of four chemical compounds ‹ adenine, cytosine, guanine and thymine.

In people, the strand is divided into 23 sets of beads, or chromosomes.

The task of deciphering the human genome has been to determine where each chemical compound appears on each chromosome. It's required hundreds of scientists to use hundreds of computers that perform billions of computations. It's taken them a decade.

The team announced completion of 90 percent of its work in June 2000, five years ahead of schedule.

Roe said the remaining holes and gaps will be finished two years from now, in time for the 50th anniversary of Watson and Crick's DNA discovery.

He hoped the Human Genome Project would be exciting to the public, but he never thought it would be so widely embraced.

Though sequencing the genome is only the first step, the promise it holds for future breakthroughs in fighting cancer and other diseases has energized the nation's hope.

For years, Roe worked in his laboratory, like many scientists, virtually unnoticed by the outside world. Now, the researcher is in demand. Phone calls, visitors and trips across the country compete for his time.

At least once a month, Roe travels to conferences or meetings, giving presentations on the genome project's findings and its implications for future research.

The human genome was always something that the professor wanted to teach and research because it was interesting.

"You never know how important it is until you do it," Roe said. "This has by far and away exceeded my expectations about how well-recognized it would be for its significance."

Roe earned his undergraduate degree in 1963 from Hope College in Michigan and completed his master's and doctoral work at Western Michigan University in 1970. He served on the faculty at Kent State University in Ohio before moving to the University of Oklahoma in 1980.

Shortly before moving to OU, Roe spent a sabbatical in the Cambridge, England, laboratory of biochemist Frederick Sanger, winner of the 1980 Nobel Prize in chemistry for his breakthrough work in sequencing DNA.

Roe was there when Sanger's team developed the prize-winning method for mapping the structure and function of DNA. Again, Roe was inspired, and he has been sequencing DNA since.

OU microbiologist Joseph Ferretti was among the first in Oklahoma to learn the newfound DNA sequencing techniques from Roe.

In 1981, there were no automated sequencers, Ferretti said. The job was done manually, using radioactive material and taking weeks to do what can now be done in a matter of hours.

In 1990, Ferretti helped Roe became one of the first five researchers in the country to get an automated DNA sequencer, through a grant from the Presbyterian Health Foundation in Oklahoma City.

In return, Roe's lab in Norman became a cornerstone of genome research at OU.

In 1995, Roe, OU Health Sciences Center microbiologist David Dyer and Ferretti became the first scientists to receive funding for bacterial genome research from the National Institutes of Health. Since then, Roe, Dyer, Ferretti and OU Health Sciences Center microbiologist John Iandolo have won government funding for three additional bacterial genome projects.

Through their work, OU has emerged as one of the world's leading public institutions in bacterial genome research.

"Bruce has worked his rear end off to build a program that is a source of pride for the university," said T.H. Lee Williams, OU's vice president for research.

"He has made it possible for OU to get into the arena of functional genomics."

Roe's lab will be the hub of a new center for functional genomics research that Williams is working to build at OU's research park on the southern edge of the Norman campus.

The estimated 40,000-square-foot building would house Roe and several other scientists whose research relates to genes and how they work.

Functional genomics is a new area that is just coming together now that the human genome has been mapped, Williams said.

Roe said the new building will solve space problems that have plagued his lab for years. Today, his 80 lab workers, computers and gene-sequencing machines occupy the 8,000-square-foot third floor of OU's chemistry building.

The new project probably will not be finished until after Roe's current mouse genome research is complete two years from now.

Roe is in the second year of a three-year, $15 million project funded by the National Institutes of Health.

Mapping the genome of the mouse is the next step of the Human Genome Project, Roe said. He and his colleagues are looking for genetic similarities between mice and people, which will be key to future medical research.

Roe said genomic research is expanding to include the rat, the chimpanzee, fish, agriculture animals and plants.

Roe plans to start mapping the alfalfa genome next month.

For more than 20 years, Roe has been doing human genome research, and the horizon for future work has only gotten wider.

"We want to know everything we can about nature, and we now have the technology to do that," Roe said.



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All content copyrighted 2001 The Oklahoma Publishing Co.


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