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  • Writer's pictureHirokazu Kobayashi

Uncovering the mechanisms of life: The “LET Loop”!

Updated: 6 days ago

Hirokazu Kobayashi

CEO, Green Insight Japan, Inc.

Professor Emeritus and Visiting Professor, University of Shizuoka

It all started with observing caterpillars (butterfly larvae). Several early-stage larvae of the swallowtail butterfly (Papilio machaon) attached to carrot leaves were brought back from the field around 1962 when I was in elementary school. A mesh breeding cage about 25 cm wide, 25 cm deep, and 50 cm high was made. In this way, I kept swallowtail larvae every summer and observed the larvae molt, pupate, and finally emerge as butterflies (eclosion). The carrot leaves their food and could be replaced with wild parsley growing in the ditch next to the field by our house. This taught me that the swallowtail larvae feed only on Apiaceae. Around this time, I was thrilled to find adult (butterfly) common bluebottles (Graphium sarpedon) and great purple emperors (Sasakia charonda), as well as jewel beetles (Chrysochroa fulgidissima). In the upper elementary school grades, there was a microscope at home, and I used it mainly to observe plant cells. Microscopes at that time did not have recording devices. I enjoyed sketching microscopic observations. In university, I belonged to the plant pathology laboratory and was engrossed in elucidating the action mechanism of host-specific toxins produced by the fungus causing apple leaf spots. Sometimes, I had to walk about 3 km to the lab in the middle of the night to observe over time. Through this research, I saw the energy substance produced by organisms, ATP, for the first time and was moved by the fact that it was just a powder. I quantified ATP using luciferase activity, purchasing dried firefly tails containing luciferin and luciferase as reagents, which amazed me. In graduate school, I researched gene expression, and for the first time, I saw DNA, which looked like white fibers. In the 1970s, the analysis of genetic information encoded in DNA, the blueprint of life, became possible. I felt this would reveal life's essence and became deeply involved in DNA science. In the early 1980s, I had the opportunity to research at Harvard University, which was at the forefront of DNA biology.

The mysteries of life inside plants and animals' cells arouse curiosity. The invention of the microscope in the 1600s allowed the observation of cells and microorganisms, leading to the development of "cytology" and "bacteriology." With the advent of chemical analysis in the 1900s, the chemical components making up cells were elucidated, progressing into "biochemistry." After the 1950s, X-ray diffraction became powerful in analyzing protein structures. This technique was used to analyze the structure of DNA, the blueprint of life, which was revealed in 1953. In the 1970s, decoding the DNA genetic code (base sequence) became possible, leading to the development of "molecular biology." Gregor Johann Mendel's (1822-1884) "genetics" met molecular biology in the 1990s, giving birth to "molecular genetics." Recent advances in various imaging technologies have promoted "structural biology,” based on image analysis at the tissue and cellular levels. In this way, technological innovation supports life sciences. Science depends on analytical technology, and my research was also linked to such technological innovations.

Deriving or utilizing "principles" is "research," I am fascinated by its charm. On the other hand, "research" itself has "principles" in its methodology. These are naturally acquired rather than taught. In other words, those who excel in research methods become successful researchers. This resembles the PDCA cycle [Plan, Do, Check, Act] and the OODA loop [Observe, Orient, Decide, Act]. Research progresses through Literature review → Experiment → Theorize, repeating, and refining this cycle. I want to call this the "LET Loop," a term no one has adopted.

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