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Smithies wins 2001 Albert Lasker Award


Carolina professor Oliver Smithies is a recipient of the 2001 Albert Lasker Award for Basic Medical Research, the nation's most distinguished honor for outstanding contributions to basic medical research.

The Albert and Mary Lasker Foundation announced the award Sept. 16.

Smithies, excellence professor of pathology and laboratory medicine, shared the award with two other scientists for their pioneering work using mouse embryonic stem cells to create animal models of human disease. The other recipients are Mario Capecchi of the University of Utah and Martin Evans of Cardiff University of Wales.

The Lasker Awards have often been called "America's Nobels," and 63 researchers who have won Laskers have gone on to receive the Nobel Prize, including four in the past three years.

Chancellor James Moeser said the award is something for which the University can be proud. This kind of national recognition sheds light on the value of Smithies' work and at the same time, reflects the importance of great research universities such as Carolina.

"Oliver Smithies' work has advanced the effective treatment of many diseases, and millions of people worldwide live better and longer lives because of the talent and determination he has brought to his work," Moeser said.

"For decades, he has provided the very best kind of example to students and colleagues through his modesty, good humor, creative intelligence, compassion, resolve and love of invention.

"Through his example, our own medical students are learning the most responsible and effective ways of helping their world as researchers.

"It is only fitting that an organization as prestigious as the Albert and Mary Lasker Foundation would pay homage to his more than 50 years as a researcher -- and, more specifically, his outstanding contributions to basic medical research. We are honored that he is a member of the Carolina campus community."

In the wake of the news that he'd won the award, Smithies reflected on what it means to be a scientist.

"Non-scientists tend to view science as a dry and difficult subject, but I think it's rather like being an artist," he said. "You are making something from nothing often. You are creating a vision in your head and putting it down in the experiment. It's a composition."

The Lasker Award statement cited Smithies, Capecchi and Evans for their decades of fundamental studies in mouse embryology and molecular genetics. While Evans' work focused on tracking down embryonic stem cells, Smithies and Capecchi sought to target genes by a process called "homologous recombination."

"Homologous" describes the part of the process in which the incoming DNA sequence lines up with its twin target sequence in the chromosome. "Recombination" describes the part of the process in which the incoming and target molecules break and rejoin each other.

Depending on the technical details of the experiment, the whole process replaces one version of the gene with another or adds another copy of the gene in tandem.

The award statement, in citing Smithies' specific contributions, said:

"Smithies devised a laborious -- but extremely sensitive -- method to find cells in which gene integration occurred at a chosen location. He aimed to detect such rare cells among the many more in which the gene would occur at random sites. The winning cell would contain a single piece of DNA that carried unique features of both the input gene and the resident gene -- characteristics that had resided on two different molecules at the beginning of the experiment, but had become next-door neighbors through homologous recombination.

"Smithies sequentially divided a population of 4,400 cells into smaller and smaller pools, tracking the ones that contained pieces of DNA with diagnostic features of both the donor and recipient molecules. Eventually, he found a cell that carried the critical combination of DNA sequences on a single molecule, and published the work in 1985. His discovery showed that specific planned modification of native genes was possible. The DNA dart had found its corresponding sequence in the vast tangle of chromosomal DNA; he'd targeted a specific gene."

During his career of more than 50 years, Smithies has pioneered techniques advancing the study of ailments as diverse as jet lag, inflammation, cystic fibrosis, sickle cell anemia, heart disease and high blood pressure.

As a young child, he was drawn to the idea of "invention" and enjoyed building telescopes and radios. He attended a high school for especially bright students and won a scholarship to Oxford University. He received a bachelor of arts degree (first class honors) in physiology from Oxford in 1946, and he went on to earn his master's degree and doctorate in biochemistry from Oxford.

In the mid-1950s, at Connaught Medical Research Laboratory in Toronto, he invented a groundbreaking process -- high-resolution gel electrophoresis. This made it possible for scientists to separate proteins quickly and easily, leading to the discovery of inherited differences in the serum proteins of healthy individuals. It was a major breakthrough in genetic research.

In 1985, while at the University of Wisconsin-Madison, Smithies made the landmark discovery, for which he has been recognized with a Lasker Award, when he found out he could make planned modifications to the genome of a living cell by inserting modified DNA into the cell.

Two years later he showed that such "gene targeting" in mouse embryonic stem cells could be used to alter specific genes in the mouse genome. The use of gene targeting led to the production of so-called designer mice with mutations that model human genetic diseases -- a revolutionary step in helping scientists understand how specific diseases and drugs work.

The Lasker Awards, first presented in 1946, are administered by the Albert and Mary Lasker Foundation. In her work spanning five decades as the nation's foremost citizen-activist on behalf of medical research, the late Mary Lasker is widely recognized for her singular contribution to the growth of the National Institutes of Health and her unflagging commitment to government funding of medical research in the hope of curing devastating diseases.

Each Lasker Award winner gets an honorarium, a citation highlighting their achievements and an inscribed statuette of the Winged Victory of Samothrace, the Albert and Mary Lasker Foundation's traditional symbol of humankind's victory over disability, disease and death.

The award is quite an honor, Smithies agreed, but he doesn't want the accolades to draw too much of his attention away from his work. What people need to understand about scientists, Smithies said, is that their work is the reward.

"The part that not everybody appreciates about scientific life is that you have to enjoy the doing of it, not just what you are going to find out," Smithies said. "You have to find the sort of science where every day you get enjoyment. It's just not some enjoyment from some great discovery that you probably aren't going to make anyway. If you're waiting for that great discovery, you're likely to be disappointed.

"If you enjoy the science, you have something to look forward to every day."

He has done his work at Carolina since 1988. At the age of 76, the pull of the work is as strong to him as it ever was. And he is grateful.

What being a scientist means, Smithies said, is captured in these words once spoken to him half a lifetime ago by a cherished mentor, the late Alexander "Sandy" Ogston: "For science is more than the search for truth, more than a challenging game, more than a profession. It is a life that a diversity of people lead together, in the closest proximity, a school for social living. We are members one of another."

The words, first spoken in 1970, mean so much to Smithies that he has them on a piece of paper. He's carried those words in his wallet for years and shared them with a countless number of his students.

As he sees it, "There is no better description of what science is about and what the life of a scientist is about."


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