In Japan, with its rapidly advancing graying and low birth rate, it is anticipated that there will be a rapid increase in medical costs coupled with remarkable progress in medical technology and medical needs, and at the same time the need for nursing care will also increase. Furthermore, on the other hand, there has been a definite decrease in the number of working young people, and how to safeguard the elderly and their home life, as well as how to respond to a steep increase in medical costs, is becoming a major issue of concern.

　Generally, diseases which deteriorate the health of the elderly and create the need for nursing care have genetic causes in the background and appear due to a long-term complex relationship with environmental factors. Consequently, it has been very difficult to identify the cause and mechanism of the disease. Moreover, these diseases are difficult to completely cure once they appear, there are many cases where the disease gradually progresses and results in serious complications, threatens the patient's life, and requires nursing care. The issue of how to deal with these diseases that accompany aging is of utmost importance in Japan, where the birthrate is declining and graying is advancing. Under these circumstances, calls have been made for the importance of prevention, but preventative medicine thus far has mainly taken the approach of identifying disease risk factors and getting people who are deemed to be high-risk to avoid them.

　In recent years, advances have been made in research regarding the relationship between individual variation of the human genome and diseases, and gradually more is becoming known about disease-causing genes. Also, progress is being made in research on identifying how the environment during the fetal stage and after birth influences the onset and development of disease. In addition, it has been observed that in diseases accompanying aging, in many cases certain pathological changes have already taken place during the pre-onset asymptomatic phase. On the other hand, in regards to the biomarkers1 which serve as an index for the development of disease, rapid advances are being made in research on biochemical findings such as proteins and RNA, and signs from imaging, etc as well. Due to such progress in life science, it is becoming possible to diagnose several diseases during the pre-onset asymptomatic phase (henceforth, the "pre-symptomatic phase"). Consequently, biomarkers, different from previous prevention methods, will be used to predict the onset of disease at high probability, and a new medical science which focuses on its target of therapeutical interventions at an early stage is expected to become a reality in the near future.

　Taking the aforementioned background into account, this initiative proposes preemptive medicine as a new direction for medical science with the aim of diagnosing, predicting and treating disease with a high degree of accuracy in the pre-symptomatic phase even when there are no clinical symptoms and no abnormalities are detected in routine medical check-up, and furthermore, proposals for research and development issues based on this idea that should be taken up by the government at the earliest possible opportunity are summarized as the following four issues. Although there are some differences for each disease, basically, these issues are common to all diseases.

Issue 1: Identification of the cause and mechanism of disease
Issue 2: Search and discover candidates for biomarkers and seeds for treatment technologies
Issue 3: Narrow down the candidates for biomarkers and seeds for therapeutic treatment technologies and assess their safety and usefulness
Issue 4: Appropriate provision of preemptive medicine (giving the results of our research back to society)

Issue 1 is the foundation for all of the issues described above, and from the viewpoint of preemptive medicine it promotes genetic, molecular biological, biochemical, cell biological research regarding the development of disease, as well as various types of clinical research to understand the interaction of genetic factors and environmental factors, with epidemiological research, including cohort research in particular. In Issue 2, in order to narrow down the group of biomarkers, that enable us to diagnose patients in the pre-symptomatic phase and in order to assess the usefulness and safety (effects and side effects of drugs, etc.) of seeds that can be applied for a therapeutic intervention, we will thoroughly and systematically search for biomarker candidates and treatment technology seeds. Specifically, data obtained from "omics research" (genomes, epigenomes, transcriptomes, proteomes and metabolomes, etc.), imaging diagnosis such as molecular imaging, and epidemiology will be analyzed. In Issue 3, the reproducibility, usefulness, and safety of the biomarker candidates and treatment technology seeds will be verified. For this purpose, in human trial ? namely clinical research ? under scientifically acceptable conditions will be conducted on a large number of people. In Issue 4, we will conduct a scientific examination on advancing the propagation and establishment of preemptive medicine in society. As preemptive medicine means performing examinations and treatments on people who are in an asymptomatic state in which clinical symptoms have yet to appear, it is essential to deepen their understanding of its necessity. The methods in which the biomarkers and treatment seeds developed in Issue 3 will actually be used will be considered based on statistical, economic, and sociological analysis. As for the therapeutic tools, compliance (patient compliance with doctor's instructions), cost effectiveness, and possible side effects will also be considered. Furthermore, as a measure toward social acceptance, systematic and behavioral medical research will also be conducted to examine the improvement of medical literacy and behavioral modification, and examining how the costs should be shouldered, etc.
　The aforementioned research will be promoted by many players: basic research centered on academia (mainly Issues 1, 2), applied research and development via collaboration between the private sector, academia and government involving industry (mainly Issues 2, 3), clinical research centered on hospitals (mainly Issue 3), and applied research by the national and local governments, academia, medical facilities, insurers, industries, NPOs, etc., in order to create acceptance and establishment of new medical technologies in society (mainly Issue 4). With this as the foundation to proceed effectively and efficiently, strategic collaboration with existing cohorts based on long-term vision and the design of new cohorts, as well as the formation of clinical research support centers should be promoted together. Furthermore, as the development and application of new medical technologies requires a comparatively long period of ten years, the timeframe of this initiative as a whole should be estimated at around twenty years.

　As diseases for case studies for preemptive medicine, this initiative will take up Alzheimer's disorders, Type 2 diabetes, osteoporosis, and breast cancer, and organize the issues that should be engaged taking the present state of each disease into consideration. The details are as described in this document.

　In conclusion, when the aforementioned preemptive medicine is made a reality, a new medical science entirely different from what has existed thus far will be born, and the development of various related medical technologies will give birth to large industrial profits. At the same time, if many people are able to lead long, healthy lives, not only will this result in a reduction in medical and nursing care costs, a high-quality life can be ensured, which is something of immeasurably great value. The advancement of preemptive medicine holds the promise of creating large social and public value in addition to industrial and economic value advocated by innovation. This value can be called the "fourth value," as opposed to the ones that accompany primary agricultural or natural products can be called the "first value," the ones that accompany industrial production can be called the "second value," the ones that accompany intellectual property rights can be called the "third value." This is because the fourth value will greatly contribute to people leading longer, healthier, and higher-quality lives.