Overview of 2024 and Prospects for 2025

2024 was a turbulent year that began with a devastating earthquake on the Noto Peninsula, which blew away the festive atmosphere of the New Year. Following the earthquake, Noto was hit by other disasters including heavy rains, and many people experienced great hardships. Even now, a year later, my heart aches when I think of the many people who are still living in evacuation shelters.

The war between Russia and Ukraine has been going on for almost three years, and there are signs of further escalation. The situation is bleak for the citizens who desire peace, with little hope in sight. The Israeli-Palestinian armed conflict in Gaza has entered its second year, with over 40,000 deaths and 100,000 injuries. 90% of the residents in the area have been forced to evacuate. The images of children suffering from serious injuries and severe food shortages tear at our hearts, making us feel helpless being so far away. We, as global citizens who yearn for world peace, need to seriously think about what we can do to end such tragedies as soon as possible. In this regard, the awarding of the 2024 Nobel Peace Prize to Nihon Hidankyo, an organization of survivors of the 1945 atomic bombings of Hiroshima and Nagasaki, gives us hope for the possibility of nuclear disarmament.

At the institute, we also faced personal tragedies. On July 23, our Chairperson, Keiji Tanaka, passed away. Tanaka sensei was a great researcher and a pillar of the institute, and his sudden departure from our midst was deeply shocking. Even now, after nearly six months, tears well up every time I see the door to his office. In March, Deputy Senior Researcher Ito Kawakami, in the Molecular Pathology and Histology Analysis Laboratory, also passed away making it a year of sad events for the institute.

Progress in the Life Science in 2024

In 2024, there were many news stories that delighted the Japanese people, such as Shohei Ohtani’s 50-50 achievement and the outstanding performances of Japanese athletes at the Paris Olympics Games. What about the field of science? The 2024 Nobel Prize in Physiology or Medicine was awarded for the discovery of microRNAs, which play crucial roles in the regulation of gene expression. MicroRNAs are involved in cancer formation and aging of humans and will be important tools for the development of diagnostic and therapeutic measures for these diseases/phenomena. RNAs similar to microRNAs had previously been identified in Escherichia coli. The replication origin region of the drug-resistant plasmid R1, which I studied during my master's and doctoral programs, codes for a short, functionally unknown anti-sense RNA called CopA, and subsequent research revealed that CopA RNA controls the translation of proteins necessary for replication initiation. The replication of bacterial vectors (e.g. pUC18 and pET plasmids) widely used for cloning and expression is also controlled by a short anti-sense RNA called RNAI, and Dr. Junichi Tomizawa, the former director of the National Institute of Genetics and a member of the National Academy of Sciences, recognized the importance of RNAI and elucidated its mechanisms of action in the 1980s. The discovery of microRNAs in higher eukaryotes clearly demonstrates that the most important principles and mechanisms of life are always conserved throughout evolution.

The Nobel Prize in Chemistry was also awarded for work that deeply affects our research. The prize was awarded for the development of technologies for predicting protein structures and for designing proteins with new functions. Accurate prediction of protein structures by AlphaFold has become a routine research method. In particular, with the announcement of AlphaFold3, it has become possible to accurately predict the formation of protein complexes with various ligands such as nucleic acids and lipids, revolutionizing life science research.

There were many other discoveries in 2024. For example, research towards the development of drugs that enable rejuvenation has been advancing worldwide. Senolysis, which removes senescent cells, and reprogramming, which rejuvenates senescent cells, are two promising approaches for rejuvenation. The concept of “anti-aging,” which delays aging and extends lifespan, has become a realistic possibility, leading to investments of hundreds of billions to trillions of yen by foundations and individual investors. However, it may be difficult to extend the maximum human lifespan beyond 120 years. What is currently most sought after is how to extend healthy lifespan.

In our institute, we conducted a two-year seminar series on “Aging and Health” and invited renowned researchers in aging research to give lectures. After more than 20 excellent lectures, healthy aging ultimately came down to the three fundamental principles that everyone has known for decades: having a proper diet, getting quality sleep, and engaging in moderate exercise. Whether anti-aging drugs contribute to extending healthy lifespan is still unknown, but we may have the answer in 10 years.

Outlook of TMIMS for 2025

At the Tokyo Metropolitan Institute of Medical Science, our mission is to “elucidate the causes of major diseases and develop preventive and therapeutic measures through innovative and original medical discovery. This will help improve health, medical care, and welfare, thus protecting the lives and health of the citizens in the Tokyo metropolitan area.” We have been pursuing a combination of “basic medical research aimed at unraveling the mechanisms of life” and “practical medical research directly related to diseases”, aiming for impactful results and early social contributions. We are currently at the end of our fourth project term (from fiscal year 2020 to 2024). In the upcoming fifth project term, which begins in April of 2025, we will continue to promote research with the same philosophy as the previous term. We have recently decided to add three new projects and have recruited three excellent new project leaders, who will start their research in 2025. Our institute aims to provide an environment where individual researchers’ original ideas are respected and can flourish, supported by excellent research facilities and research support. Furthermore, we strive to advance “comprehensive” medical research from the cellular level to animals, people, and society. To achieve this, we promote free and open communication within the institute and support an environment conducive to productive collaborations in a harmonious atmosphere. Fortunately, the COVID-19 pandemic is finally over (although we must remain cautious as infections are still occurring—I was infected for the first time last year in July and experienced a month of pain, personally making me realize how COVID is different from the common cold). This has allowed various inter-departmental gatherings to take place. Last year, with the assistance of the Tokyo Metropolitan Government, we obtained an Orbitrap Exploris 480 mass spectrometer, enabling us to perform advanced mass analysis at the institute. Moving forward, we intend to further enhance the diverse research technology support system required for creative medical research.

In 2020, we established the “Research Center for Genome & Medical Sciences” and the “Research Center for Social Science & Medicine” to support the Tokyo Metropolitan Government’s health, medical care, and welfare initiatives. However, as we learned from the toll caused by the COVID-19 pandemic, we also need to be prepared for unpredictable emergencies and will start the “Research Center for Infectious Diseases” in April of 2025. This new research center will conduct research on the mechanisms of various infectious diseases, focusing on those selected by the Health Science Council. Goals of this center include the development of antiviral drugs based on natural immune mechanisms and the generation of universal vaccines. In times of emergency, the institute, including the Research Center for Infectious Diseases, the Research Center for Social Science & Medicine, and the Center for Medical Research Cooperation, will work together as a whole to swiftly establish a system that can respond to infectious diseases. We will closely collaborate with the Tokyo Metropolitan Institute of Public Health, the Tokyo Center for Infectious Diseases Prevention and Control (iCDC), and metropolitan hospitals to understand emerging pathogens, elucidate infection mechanisms, understand immune responses, and conduct research on epidemiology.

Sciences in Japan

Recently, there has been heated discussion regarding the decline in Japan’s research capabilities. Although the total number of papers is increasing, there is a decrease in the number of top 10% papers that are frequently cited and have high academic value. While there have been various arguments and multiple reasons proposed for this decline, one reason could be the decreasing attractiveness of pursuing research as a career, leading to talented students not choosing to become researchers. Many researchers still experience the joy of making discoveries and find excitement in research, but unfortunately, many students leave the research path before experiencing this joy. Moreover, witnessing senior researchers struggling to find jobs and being unable to fully focus on research due to time-limited positions may make students think, “I don’t want to end up like that.” Publishing papers in top journals is an aspiration for researchers, but the bar for achieving this is exceptionally high. Having a paper accepted in a top journal requires logically compelling content, multiple different experimental approaches to support the conclusions, and researchers who can persevere despite constant pressure and setbacks. The cultivation of successful researchers requires support for research systems that enable diverse experiments required for goal achievement and funding review systems that support long-term research necessary for groundbreaking findings. In Japan, these systems need significant improvement. Regarding funding reviews, it is necessary to establish a system that accurately assesses the proposed content, provides opportunities for feedback and resubmission based on comments, and supports research proposals with a high potential of scientific value.

Currently, Japan has high expectations for Nobel Prize laureates, and indeed, many laureates have emerged in the past 20 years or so. Many of these prizes were awarded for curiosity-driven research, which received support 30 to 40 years ago. Basic research is the root of “the tree of science,” and as long as the roots exist, new buds will always sprout and flowers will bloom. However, it seems that the current science policy in Japan focuses too much on the flowers that are about to bloom, neglecting the invisible, but essential roots. If this continues, there is a possibility that in 10 or 20 years, the tree of science will fall and no flowers will bloom. The roots need to be nurtured for the coming decades, and as long as the roots grow stronger, the flowers and fruits will also grow. In order for Japan to continue leading the world in the development of science and technology in the coming years, it would be necessary to continue supporting basic research that nurtures the roots.

Wishes for 2025

The zodiac sign for 2025 is “Kinotomi” in the Japanese zodiac system. “Kinoe” represents the second Heavenly Stem and symbolizes the energy of the Yin Wood element. It signifies flexibility, cooperation, and the ability to progress towards personal goals while maintaining harmony with the surroundings. “Mi” represents the sixth Earthly Branch, which is the sign of the Snake. The snake is known for its strong life force and for its ability to heal surface wounds through the shedding of its skin, symbolizing resurrection and regeneration. In 2025, which marks the beginning of a new project, we anticipate the germination and growth of new seeds while reaping significant fruits from the trees nurtured during the previous project term.

During the transition to the new year, there have been many changes in leadership in both Japan and the United States. We find ourselves in an uncertain and challenging era, where predictions are difficult and a vague sense of anxiety lingers. Albert Einstein once said, “Peace cannot be kept by force. It can only be achieved by understanding.” Unfortunately, the world peace that I prayed for in my previous year's message has not been realized. In 2025, we hope for people to come together, understand each other through dialogue, and restore peace.

For the zodiac information, I referred to the following website:
https://www.quocard.com/column/article/eto2025/
The quote from Albert Einstein was referenced from the following website:
https://news.yahoo.co.jp/expert/articles/65f921791897fc22d9594deddb3bb334c9dd6608