Nobel-Prize winning geneticist speaks at VCU

Nobel Laureate and geneticist Dr. Oliver Smithies spoke of the importance of perseverance and chance opportunity in his lecture Tuesday, illustrating clearly the trajectory of his life and career through the notes he shared with students and faculty.

“This is a truly outstanding scientist who should have won three Noble Prizes,” said Dr. Paul Fisher, chair of the VCU Department of Human and Molecular Genetics.

Smithies was awarded the Nobel Prize in 2007 with two colleagues for his work in gene targeting in mice, a method of genetically modifying the animal using embryonic stem cells.

His influential work gave scientists the ability to delete, or knockout genes of interest from mice, modifying them to create models of human diseases for study.

“It’s a fantastic technology for all of us who have utilized this in approaches to genetically modifying animals and understanding true biology in vivo,” Fisher said.

Smithies’ influence in genetics and molecular science is clear, according to VCU professor of forensic Science and biology Tracey Dawson Cruz, who was a graduate student under Smithies.

“I don’t know any other living scientist that has made more technological contributions to the field of molecular biology,” Cruz said.

Smithies work led to a better overall understanding of the causes and development of many major human diseases, but he says genetics was not always such an optimistic field.

He recalled visiting the clinic of fellow geneticist Norma Ford Walker in the 1950s, where she studied and treated children with genetic diseases.

“They were actually rather depressing, because geneticists couldn’t do very much at that time,” Smithies said. “All they could do is tell what the risk was of something happening.”

On one such visit to the children’s clinic, Smithies met a small girl with cystic fibrosis, who he says he truly lamented not being able to help.

“Fortunately, it’s changed enormously, because now we can do things,” Smithies said. “We can advise a family. And of course we can do much more in helping to treat.”

Smithies was vital in developing the field of genetics, especially through his discovery of homologous recombination.
Homologous recombination is a technique in which two identical or similar strands of genetic material are broken and then joined together to produce genetic variation or repair defective genes.

Though the frequency of success was very low with his initial experiments in the mid-1980s, Smithies’ published study showed that the planned modification of a specific human gene is possible in a living cell.

“That changes the framework, because now the scientific community knows that gene targeting is possible,” Smithies said.

Most recently, Smithies work in gene targeting has been focused on more common quantitative human conditions, like cardiovascular disease, rather than rare gene-knockout diseases like cystic fibrosis.

At the end of his lecture, Smithies offered some advice to students.

“It’s very important that you enjoy what you do,” Smithies said. “If you find you’re doing something that you don’t enjoy, go to your adviser and ask for a change.”
Smithies said that approach usually works.

“And if it doesn’t, there is another solution . and that’s change your adviser.”