His most important achievement to date is the establishment of comprehensive animal experimentation systems using strictly defined laboratory animals to assure reproducibility of experimental results in medical research. Before his concepts were applied, it was generally considered to be very difficult or even impossible to obtain reproducible results in medical research using laboratory animals, mainly due the traditional consensus that the animals are living organisms with individual differences. He has completely changed this out-dated paradigm in medical research by establishing comprehensive animal experimentation systems. One of the factors that affects the reproducibility of the results of animal experiments is the proximate environment in which the experiment is performed including the temperature and humidity of the animal room, the size of cages and caretakers. The concept of the dramatype, which refers to the effects of the proximate environment on the phenotype, was introduced. Russell and Burch proposed the term "dramatype" in 1959 from the standpoint of animal welfare, but Dr. Nomura developed this concept to promote the importance of control of the environment to assure reproducibility of the results of animal experiments. Based on such systems, he has established international research collaborations to develop three animal models:
Transgenic Polio Mice - Widely used in polio vaccine neurovirulence testing as a replacement for monkeys.
Trangenic rasH2 Mice - Shortening of the carcinogenicity test period in drug development from two years to six months.
NOD/Shi-scid/IL-2Rγnull Mice - New generation of extremely immunodeficient mice that are the best candidate for humanized mice to date.
Application of animal ethics in CIEA
CIEA has developed animal experimentation systems based on the concept "scientific animal experiments with reproducible results can not be achieved unless the experiments are performed ethically with the animals maintained in a normal state." To this end, the 3R principle proposed by Russell and Burch in 1959 was adopted. By using animals under strict quality control and controlling the environment so that the animals are not subjected to stress, it is possible to reduce the number of animals used in experiments. It is also possible to prevent infections such as mouse hepatitis or Sendai virus through periodic monitoring of the microbiological status of animals for early diagnosis and quality assurance and to minimize discomfort of the animals. These policies are intended to maintain the animals in a normal state by minimizing stress. If the animals are not maintained in a normal state, reproducibility of results of experiments on animals as "living measuring instruments" cannot be assured. A system has been established in which mice with the human polio virus receptor introduced replace monkeys, which are closest to humans, used in neurovirulence testing of live polio vaccine. The number of animals used can also be reduced by using mice subject to stricter quality control than monkeys. "Replacement" refers to a "switch to research not using animals" but a "switch to a method not using phylogenetically higher animals such as monkeys" is a method of natural protection. Using this alternative we succeeded in reducing the zoonotic risks for investigators.
Central Institute for Experimental Animals (CIEA)
Dr. Nomura is currently Director of the Central Institute for Experimental Animals, Japan, that he founded in 1952, to improve the level of medical research.
