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Analyzing the behavior of living organisms at the atomic and molecular level... My specialty, nanobiotechnology, is a new research field that was born from the fusion of nanotechnology, which has been developing rapidly in recent years, and biotechnology, which has accumulated a wide range of knowledge over the past several decades.

Nanotechnology is a technology that allows for the creation of new materials and devices with new functions by freely manipulating matter at the nanometer (one billionth of a meter) scale, in other words, at the "scale of atoms and molecules."

The concept of nanotechnology was born in 1959. It was during a lecture given by American physicist Richard Feynman, who won the Nobel Prize in Physics, at the American Physical Society. In his lecture, titled "There's Plenty of Room at the Bottom," Feynman pointed out that it was possible to manipulate atoms and molecules one by one. In 1981, the Scanning Tunneling Microscope (STM) was invented, making it possible to directly observe atoms and molecules, which led to a major leap in nanotechnology. In 1990, IBM Zurich Research Laboratory used the STM to move atoms one by one and successfully draw the three letters "I, B, M." Although it is still far from being put to practical use, it is now theoretically possible to "assemble atoms one by one."

At the time, I was studying as a research assistant in the Department of Physics at the University of Minnesota, and it took me six years to build my own STM. I then used this STM to successfully create aluminum nanostructures, achieving research results including publishing a paper on the subject. During these days, I began to wonder if I could use this technology to conduct new research that could become my life's work. After asking myself this question over and over again, I came up with the idea of the mysteries of life.

In nanotechnology research, various techniques are used to bond molecules together, but even connecting just two molecules requires a long time. However, the atoms and molecules in living organisms bond together in a natural way. The mechanism behind this is truly "mysterious." Therefore, I wanted to take on a new challenge: analyzing biological phenomena using the "technology for observing atoms and molecules with STM" that I had developed up to that point.

Just then, I learned that there was a group in the Department of Molecular Biology at Harvard University that was conducting research combining nanotechnology and molecular biology, so I applied for a position and decided to continue my research at Harvard. This was my first encounter with nanobiotechnology.

So what kind of research is currently being conducted at the cutting edge of nanobiotechnology? Let me introduce you to some examples.

In the world of biophysics, the mechanisms of living organisms are becoming clearer at the atomic and molecular level. For example, it has become clearer that DNA, which carries genetic information, has a "double helix structure," that the characteristics of genes are determined by the combination of four types of bases (adenine, thymine, guanine, and cytosine), and that the entire genetic information of an organism (genome) is created by that DNA. DNA molecules are long and flexible, like "strings." Human DNA is about 2 nanometers thick, and if all the DNA in a single cell were connected together, it would reach a length of 2 meters.

In recent years, it has been said that it is possible to conduct experiments using "nanopore technology" that would allow DNA to be passed through an artificially created tiny hole (nanopore) with a diameter of a few nanometers and analyzed at the single molecule level. It is expected that this experiment will be used to develop a new method for determining DNA base sequences with high efficiency. In other words, a "DNA scanner" will be created (Figure 1).

The currently widely used method of DNA analysis involves first making copies of the DNA and then statistically deciphering the copies. This method has problems, such as the need to make many copies of the DNA first, which takes time and requires special reagents.

However, nanopore technology requires only a single DNA strand, eliminating the need to make copies. The decoding speed is estimated to be less than one millisecond (one thousandth of a second) per base. If multiple devices are used to decode the 3 billion base sequences of human DNA in parallel, it is possible to analyze all genetic information in about one day. In addition, no special reagents are required, which helps reduce costs.

Using this analysis technology, it will be possible, for example, to install a dedicated small device on a smartphone and store one's own DNA sequence as data on the device. This technology is not only expected to enable early detection of disease, but also to contribute to the development of new medicines and regenerative medicine.

However, current nanopore technology is not capable of reading human DNA, which is two meters long, in one go. In order to stretch the intricately entangled DNA into a single strand and guide it into the nanopore, it is necessary to find the optimal environment, including the composition of the solution in which the DNA should swim and the level of electrical stimulation to be applied. We are currently conducting research to achieve this.

When we observe the biological activities of living organisms at the molecular and atomic level, we are once again amazed at how perfect everything is, without a single error.

I wanted to take on the challenge of analyzing life phenomena using "technology to observe atoms and molecules"... With this in mind, I expanded the scope of my research and began working directly with cells. The structure inside a cell is perfect and there is no waste. This intricate system is clear when you look at the mechanism of the "flagellar motor" revealed by Professor Keiichi Namba of the Graduate School of Osaka University.

E. coli swims through water by rotating its spiral flagella at high speed. The rotation speed reaches 300 times per second. And yet, unlike a car engine, it does not generate heat, so there is almost no energy loss. And what is surprising is its size. The motor, about 30 nanometers in size, is, as Professor Namba says, "the smallest and most powerful motor in nature" (Figure 2). The flagellar motor is made up of complex molecules made up of proteins called MotA/B, MS ring, and C ring, each of which functions as a single motor by combining as "parts." If any one of these parts is missing, the motor will not function.

When I first observed this structure, I was impressed and thought, "This is what we call 'perfection.'" Living organisms can easily create such minute and intricate systems through a process known as "self-organization."

I would like to study the remarkable structures of living organisms, such as the flagellar motor, and see if we can imitate them artificially.

There are still many things that remain to be elucidated about the "roots" of life science. However, with the advancement of nanobiotechnology, I am sure that someone who will unravel these mysteries will appear in the near future. I continue my research with the aim of making "discoveries that will rewrite the textbooks." I hope that you too will develop the habit of always asking yourself, "Is what I understand now true?" without being bound by "common sense of the past." It is this attitude that makes science even more interesting.

(Published in 2015)