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Pioneering Researcher Reflects on the Past and Looks to the Future

Dr. Susumo OhnoAn article published in Cancer Center Research Report, Spring/Summer 1996, pp 13-15, by City of Hope Clinical Cancer Research Center and the Beckman Research Institute.
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Pioneering Researcher Reflects on the Past and Looks to the Future

–Susumu Ohno, DVM, PhD, DSc, Distinguished Scientist, Retires from City of Hope

There are leaders as well as followers; then there are pioneers. One such pioneer is Susumu Ohno, DVM, PhD, DSc, distinguished scientist in the Division of Biology at City of Hope’s Beckman Research Institute. In March, Dr. Ohno announced his retirement from City of Hope, bringing to a close an association that has lasted more than 40 years. While at City of Hope, Dr. Ohno made seminal contributions to the field of modern biology-contributions that have garnered him international recognition and distinction. A scientist to the core, he emphasizes that although he is retiring from City of Hope, he is continuing his many scientific pursuits with collaborators worldwide.

“I consider Dr. Ohno to be one of the world’s most creative scientists and the key ‘founding father’ of the genetics, molecular biology and immunology programs at City of Hope,” states Arthur Riggs, PhD, chair of City of Hope’s Division of Biology. “One of the lesser known facts about Dr. Ohno’s career,” he adds, “is that he understands cellular immunology better than most specialists in that field.”

In a recent interview, Dr. Ohno took time out of his busy schedule to reflect on his career and to talk about his individualistic approach to science-an approach he feels is a hallmark of his success. As his story unfolds in his own softly spoken words, it becomes clear that here is a scientist with a will of steel and an unswerving belief that nothing is accomplished by following the beaten path. Throughout his life, he has chosen instead to follow his inner compass, paving new ground as he goes.

“My father worked in the Japanese government,” he recounts, “and my parents hoped that I would follow in his footsteps.” Instead, Dr. Ohno chose to follow his passion for horses, which he developed at a very young age. “I wanted to be a veterinarian, so l enrolled in the veterinary school at Tokyo University of Agriculture and Technology.”

It was in veterinary school that Dr. Ohno first became interested in genetics due to his realization that most health problems with horses were the result of bad breeding. After earning his doctorate of veterinary medicine degree, he pursued his new interest in genetics by entering a graduate program at Hokkaido University in Sapporo, Japan, where he earned a doctorate in pathology and a doctorate of science in cytogenetics.

Dr. Ohno was 25 years old and a postdoctoral fellow at the University of California Los Angeles (UCLA), when he came to City of Hope in 1952. One of his professors at UCLA was beginning research at City of Hope, and Dr. Ohno was recruited to join him in the Department of Experimental Pathology as a research associate.

Shedding Light on the X Chromosome

Seven years after joining City of Hope, Dr. Ohno made his first important contribution to science. For 10 years, scientists had sought to understand the Barr body, a unique chromatin body found only in females and discovered by M. L. Barr and E. G. Bertram in 1 949. Dr. Ohno, in 1959, shed light on this mystery when he demonstrated that the Barr body was an inactivated X chromosome. This discovery, in turn, helped explain another puzzling phenomenon.

In mammals, sex is determined by the X and Y chromosomes; the female being XX and the male being XY. This means that females have twice as many X-linked genes as males. However, females do not produce twice as many X-linked gene products, or proteins, as males. The theory of the inactivated X chromosome, as set forth by Dr. Ohno, explains this phenomenon.

Later, the young City of Hope scientist was involved in developing what has become known as “Ohno’s Law,” the notion that the X-linkage group-the region of the X chromosome that contains genes that have no counterparts on the Y chromosome-is conserved in placental animals such as humans, horses and most common mammals. “For example, hemophilia A and B primarily affect males in humans, dogs and horses,” he explains, “because these genes are on the X chromosome in every mammalian species.”

Laying the Theoretical Foundation for Genetic Evolution

Dr. Ohno’s greatest contribution to science, because of its broad implications for biology and evolution, is described in his 1970 book, Evolution by Gene Duplication, in which he resolved the conundrum of how new genes evolve. He says this problem was particularly challenging because it addresses a phenomenon that cannot be observed. However, he adds with a smile, “I enjoy the satisfaction of solving intellectual puzzles.”

To construct his theory, Dr. Ohno had to tread new ground and hypothesize the existence of extraneous duplicate DNA. According to his theory, in order for an organism to evolve, having extra copies of genes is essential. For example, he explains, an individual has a gene for protein A, which is necessary for a certain biological function. Protein A is very similar to protein B, which the individual does not currently produce but which would be beneficial. Because of this similarity, a mutation in the gene for protein A could easily produce a gene for protein B. If the individual has only one copy of the gene for protein A, its offspring could not survive such a mutation, because they could no longer produce the needed protein A. However, if the individual has more than one copy of the gene for protein A, then its offspring could survive such a mutation because they would still have a copy of the original gene. They would produce both protein A and B. The more copies of a given gene an individual possesses, Dr. Ohno adds, the more opportunity for beneficial mutations leading to the evolution of new proteins. Because much of its tenets have been proven true, his theory of evolution by gene duplication is now widely accepted in the scientific community.

The Freedom to Be a Pioneer

Dr. Ohno feels he has been able to accomplish so much because he has been free to follow his intellectual curiosity into new avenues of thinking. “The intellectual freedom I have been accorded at City of Hope has been wonderful,” Dr. Ohno says, adding that this atmosphere of freedom has helped him explore new scientific thought and encouraged him to stay at one institution his entire career. In addition, “City of Hope was an isolated paradise,’ he says. “I came to City of Hope when Samuel Golter was executive director. He really believed that everyone under the sun is created equal. That’s the reason I stayed here.”

Dr. Ohno’s accomplishments have made him an internationally recognized scientist with over 350 papers published in leading scientific journals in the United States, France, Brazil, Greece, Italy and Denmark. In 1992, he was elected a foreign member of the Royal Danish Academy of Sciences and Letters, a highly selective group comprised of distinguished scientists, many of whom are Nobel Prize f recipients. As an additional honor, he was informed of his election through a personal telephone call from the queen of Denmark. His other awards include the Armory Prize for Reproductive Biology from the American Academy of Arts and Sciences in 1981; the Kihara Prize Award from the Japanese Society of Genetics in 1983 (Kihara was an internationally respected geneticist); and the Jenkinson Memorial Lectureship at Oxford University in England. Along with his memberships in several international scientific societies, he was made a member of the United States National Academy of Sciences in 1983; is a lifetime visiting professor at Kansai Gakuin University and Tohuku University Medical School in Japan; and holds lifetime memberships in the Scandinavian Society of Immunology and the Japanese Society of Genetics.

When asked what advice he would give to a young scientist just starting out, Dr. Ohno replied, “If you want to be remembered 50 or more years from now, you have to create a new paradigm, a new way of thinking about an ‘old’ problem. Taking the unbeaten path is the only way a scientist can succeed in a true sense.”

This is advice he has taken to heart and, as he retires from City of Hope, his lifetime of success merely serves as a foundation for the busy future in science he sees ahead. He plans to continue collaborating with His Imperial Highness Prince Akishinonomiya Fumihito, second son of the present emperor of Japan, lecturing and attending international meetings-all the while enjoying his family and, of course, finding time to ride his beloved horses.