The life science and clinical research field contributes to the formation of a wide range of social issues, including health, medical care, foods and environments. Its strategic promotion has a large impact on Japan's national policies relating to that of health and medical care, and that of agriculture, forestry, and fisheries. It thus would be beneficial to understand panoramically the latest Research and Development (R&D) trends in this field both globally and domestically for the future formulation of a significant policy of R&D strategies. Under such background, the JST-CRDS, in corporation with many experts who are active at the front line of academia and industries, summarized a report compiling the results of the panoramic view survey on this field. Throughout the survey, we found out the following two strategies are important for future directions of this field’s R&D in Japan.
Strategy ① Precision Medicine based on data-integrated medical-and life science (Internet of Medical Things, IoMT)
Strategy ② Precision Agriculture and Bio-production based on data-integrated agricultural- and life science (Internet of Agricultural Things, IoAT)
<Panoramic view of the field>
The life science and clinical research field is wide, diverse and complex. It, for example, ranges from microscopic scale (e.g., atoms and molecules) to macroscopic scale (e.g., communities and societies). It also handles various issues on social implementation such as launches of new pharmaceuticals, medical devices and new crop varieties. Therefore, at the beginning of the survey, several major areas of science and engineering in this field were mapped into a framework organized based on the perspectives of subjects (e.g., animals including humans, plants, microorganisms, and data relating to them), purposes (morphological and structural analysis, functional analysis (wet/dry), or therapy and intervention (wet/dry)) and phases (from basic to applied research) of study. Then, according to this panoramic view map, the major areas were categorized into five segments, and the panoramic view survey was carried out. The five segments are as follows: Segment 1, Life, health, disease science; Segment 2, Basic technology for drug discovery and development, and pharmaceutical; Segment 3, Biometrics analysis technology, and medical equipment; Segment 4, Food production and biorefinery; and Segment 5, Health, medical, agricultural data science.
<Trend of technological innovation>
As a result of the survey, the following three major topics were found out as the interdisciplinary technological trends in this filed.
Ⅰ) Precise and novel methods: Spatio-temporal observation, manipulation, and creation of life
In terms of observation and manipulation of life, significant breakthroughs have been achieved one after another. The first example is the emergence of genome editing technology, which allows us to manipulate genomes more freely and easily than before. This technology not only has become widespread as a tool for basic research, but also has made remarkable progress in applied therapy. The second one is cryo-electron microscopy (single particle analysis) technology, which has brought about new progress in the structural analysis of proteins. This technology, which allows us to conduct elaborate structural analysis even on samples that are difficult to crystallize, has received worldwide attention from both sides of basic research and industrial applications. In addition, tissue-decolorization technology, live-imaging technology, single cell technology, simulation of the organ/cell/molecule structure and function, light-control technology (e.g., optogenetics) and artificial cell technology are noteworthy trends.
Ⅱ) Diverse and complex research subjects: Expansion of the research subjects and analysis of complex systems
Model organisms such as mouse and Arabidopsis thaliana have been being used as essential materials for basic lifescience and medical science at early stages. However, knowledge obtained from model organisms is not always applicable to other organisms in a real world including humans and crops, so efforts to bridge the gap between those are demanded. Under such circumstances, new approaches such as organoid and organ chip technologies are expected to be developed as an in vitro experimental systems for human. There are also active efforts for the technological improvement allowing genome editing technology to apply various species including humans. Traditionally, a scientific research in this field is carried out in a reductionist way focusing on individual molecules and single biological phenomena. However, sophistication in analysis technology has enabled us to analyze more complex systems. In recent years, microbiota (microbiome) analysis technologies, including metagenome analysis and metatranscriptome analysis, have made remarkable progress. Such directions trying to capture the overview of complex subjects through amalgamating experimental techniques and informatics technologies have been actively promoted.
Ⅲ) Data integration and systematization: Personalization and prediction based on integrated big data
Technologies for data are remarkably being developed. Integrative analysis of data obtained from several different analytical instruments (multimodalities) is one of trends in this area. For example, the conventional omics study such as genome or metabolome is mainly focused on a single omics, whereas recent advancement of technologies for data analysis enables to integrate different types of omics data. There is also another attempt to conduct integrated analysis on everything from molecular-level information to individual-level information. Wearable devices allow us to collect time-series data more easily, and thus temporal changes are getting familiar as subjects of analysis. The fact that integrated big data analysis is paving the way not only for elaborate description of biological phenomena but also for precise prediction is a noteworthy trend and is clearly future direction of the life science and clinical research field.
<Trends of policies in Japan and foreign countries>
The U.S. has allocated a huge budget to the life science and clinical research field and its amount is overwhelming other countries. The investment, for example, is about more than 3-trillion yen even only for NIH. There are several major national initiatives including the Precision Medicine Initiative (2015-), promoting precision medicine, Cancer Moonshot (2016-), aiming at drastically accelerating cancer research, and the BRAIN Initiative (2013-), aiming at unlocking all of the secrets of cerebral functions. The Accelerating Medicines Partnership (2014-) also has been started as an initiative under which NIH, FDA, and pharmaceutical companies are working together.
In the European Union, research in the life science and clinical research field has been conducted in the Horizon 2020 framework, and several large projects are underway, including Personalized Medicine (2014-), promoting personalized medicine as one of the Social Challenge programs, and the Human Brain Project (2013-), studying brain science as one of the Excellent Science programs. Innovative Medicine Initiative 2 (2014-) also has been started as Europe’s largest public-private initiative. In addition to such initiatives by the EU, various R&D activities are also underway in each country.
In China, as part of Science and Technology Innovation 2030, several projects including Brain Science, Breeding Technology, Environmental Protection Technology, and Health and Welfare Technology have been promoted in the life science and clinical research field. Initiatives focusing on precision medicine have also started.
In South Korea, active investments have been made in the promotion of clinical trials and the support of open innovations as part of the Second Biotechnology Development Master Plan (BIO-Vision 2016). Support for researches associated with gene therapy or stem cell therapy, development of medical equipment, and nurturing industries associated with precision medicine and regenerative medicine into key industries for South Korea has also been provided.
Recent major trends in Japan is the establishment of the Japan Agency for Medical Research and Development (AMED) in 2015. AMED invests in R&D basing on nine key projects, such as regeneration medicine, cancer, infection, brain, genome, pharmaceuticals, and medical equipment (2019 budget request: 152.8billion yen).
<Future directions of the life science and clinical research field>
As a result of scientific and technological initiatives among industry, government, and academia in countries, remarkable technological advancements have been made. This advancement allows us not only to understand biological phenomena and diseases more deeply, but also to predict them and even control them based on the prediction by using big data. Furthermore, these advanced scientific knowledge and technologies would contribute to tackling various social problems, including the Sustainable Development Goals (SDGs) adopted in the United Nations. Therefore, it is expected to consider results of this panoramic view survey and further study as necessary when a policy for R&D strategies is discussed. The three elements of the research and development strategies Japan should promote are as follows.
(1) High-accuracy understanding and prediction through the acquisition of elaborate, enormous experimental data, big data analysis, and the formulation and acceleration of a series of verification cycles in experimental systems
(2) Event control through appropriate prediction-based interventions
(3) Enhancement of research and development platforms at the start of promotion (e.g., data infrastructure (accumulation, management, and utilization), equipment infrastructure, utilization of university hospitals, human resources, regulatory science, and ELSI)
In order to promote future R&D activities in this field with integrating the three elements mentioned above, it is crucial to be intensely aware of an idea of a circulation of R&D. This idea means that new research hypothesis should be extracted from a society where new technologies were implemented, and it should lead to further promotion of basic research; the new technologies were developed based on a basic research and then evaluated and verified in a society. In order to accelerate this chains of circulation, taking data science effectively into the field would be a key driver.
Lastly, based on this survey, we propose the following two strategies as the mid-to-long term strategy Japan should promote although its details are to be studied in near future.
Strategy ①: Precision Medicine based on data-integrated medical-and life science (Internet of Medical Things, IoMT)
→ Analyze biomarkers such as genes, biomolecules, pulses, blood pressures etc., lifelogs, and environmental factors for each person in an integrated way to foresee the occurrence and progress of diseases. Avoid disease severity and recurrence by stratifying/individualizing patients with taking account of cost-effectiveness and implementing preventive intervention. Promote medical- and life science relating to this area.
Strategy ②: Precision Agriculture and Bio-production based on data-integrated agricultural-and life science (Internet of Agricultural Things, IoAT)
→ Evaluate growing environments of crops quantitatively by sensing soil, environmental conditions, microbiota, insects, and parasites to analyze the information in an integrated way. Research to develop techniques to monitor and control the growing environment and status appropriately, aiming at maximizing the quality and production efficiency of agricultural crops and products. Promote plant science and microbiological research relating to this area