We all take in fluids on a daily basis. And we all need water to survive. The average person may only survive for two or three days without liquids, and even the strongest person can only survive for a week at most. So why do we have to constantly consume water? The very existence of water comes so naturally to us that it is hard to stop and think about what makes it so essential.

Professor Masato Yasui, who leads the Department of Pharmacology at Shinanomachi Campus, has spent countless hours researching the behavior of the "water" inside our bodies, working tirelessly to understand its physiological phenomena.

"The water we drink gets absorbed into the bloodstream and then passed onto the cellular level before finally exiting the body in the forms of saliva, tears, sweat, and urine. When thinking about human physiology, water plays a crucial role," Prof. Yasui explains.

Consider disease screenings for example. When screening for diabetes, we measure blood sugar level. When testing for cancer, we measure biomarkers—substances whose presence is indicative of a specific disease—found in blood or urine. Until now, the medical sciences have examined the state of the body by looking at the concentration of specific substances dissolved in urine and blood. But by working in that way, each disease screening requires you to measure the concentration of a different substance. And in the case of diseases for which biomarkers have not yet been found, it is impossible to do anything until a reliable screening method is established.

That is where water in the body plays an important role. Let's start with some basics you may have learned in your junior high science class. A substance that dissolves in a liquid is called a "solute," and the liquid itself is a "solvent." This “body water” works as a solvent to dissolve various solutes, and in the past, the medical sciences focused on these solutes when diagnosing diseases. However, here in the Department of Pharmacology, we observe how body water works as a solvent.

"When a substance dissolves in water, it interacts with surrounding water molecules at the microscopic level, whose characteristic water absorbance patterns are affected and change ever so slightly. If you can see this change in detail, that is, measure and describe it scientifically, then you can see what is going on the body," Prof. Yasui says.

Because the role of body water as a solvent is common among all people, we can infer that all kinds of information can be obtained from understanding its changes. Prof. Yasui asserts that if this method, called aquaphotomics, which sees water as a molecular mirror, is put into practical use, may turn the common sense of medical examination on its head. Note that the aquaphotomics was initially developed by Prof. Romiana Tsenkova (Kobe Univ.).

Why did Prof. Yasui decide to focus on water? After starting his career as a pediatrician, he says that he often cared for newborns and premature babies.

"It is said that about 60% of an adult body is water, but this number can reach up to 90% in a fetus. After growing for ten months in amniotic fluid, the baby comes out into the world. Lungs that until birth were full of fluids are drained immediately after birth, allowing a newborn infant to start breathing. 19th-century German biologist Ernst Haeckel once said that the moment of birth is as dynamic as when life rose out of the water and onto the land. That’s what first got me interested in water,” Prof. Yasui recalls. "The water that fills the lungs of the fetus was thought to have been drained by the lungs being pressed when passing through the birth canal. However, it is becoming apparent that, in fact, water channel protein, aquaporin plays an important role," he explains.

"Clinical practice can feel like a game of whack-a-mole, where you deal with one symptom only to have another appear. I wanted to know how the moles were moving about underground." Prof. Yasui also says that as a pediatrician, his desire to understand the disease from a developmental viewpoint has gotten stronger. For clinical pediatricians, small differences in age can require significant changes in treatments and medications due to the body's developmental processes. It is essential for pediatricians to gain specialist knowledge of the best treatments for specific stages of development, but even then, many treatment mechanisms have yet to be fully explained.

And Prof. Yasui’s research into development has led to considerable interest in water. For example, adults can control the amount of water in their bodies through urine and sweat. You may have more concentrated urine—more solutes and less water—if you sweat a lot. But infants tend to experience dehydration and heatstroke because their bodies are not yet capable of concentrating urine due to immature kidney function. Because of this, a high proportion of body fluid, which is taken in the form of fluid from breast milk or infant formula, is excreted more quickly and in larger amounts than adults.

Prof. Yasui has begun to think that the amount of fluid in the body varies depending on the stage of development and that there is also a difference in how active water circulation is depending on the stage of development. This hypothesis has led him to begin studying the passage of water throughout the body.

Prof. Yasui says that aquaporins—the water channels within the body—are doing important work. Aquaporins are proteins that play a role as water channels that selectively pass water between cell membranes. The 13 kinds that have been discovered so far each have their own structures and functions.

"One kind of aquaporin is now thought to be responsible for absorbing the water in the lungs of a fetus into the body. A good amount of the water in our body moves through aquaporins and leaves the body as sweat, saliva, or urine. Of course, this is just the tip of the iceberg, and there are plenty of things we have yet to find out."

This brings us to Prof. Yasui’s exhaustive, in-depth research on water from a medical perspective.

How do you observe the differences in the water that circulates within the human body? Water is H2O―a molecule that contains one oxygen and two hydrogen atoms―and a water molecule exhibits particular vibrations of the covalent bond between the hydrogen and oxygen atoms in a water molecule. Changes to the pattern of hydrogen-bonding among water molecules generate changes in the vibrations, which we can measure using infrared spectroscopy, which in this case refers to the water-light interaction at different frequencies of the electromagnetic spectrum.
Additionally, this method suddenly opens up access to an entire series of wavelengths along the near-infrared spectrum. And hopefully, if we continue to accumulate this data, we should be able to conduct new analyses on all kinds of information long after measurement.

“In current MRI examinations, we can diagnose cancers and inflammations from the spin of hydrogen atoms of water inside the body. The MRI detects signals that are emitted from the ‘water’ in cancer lesions. These signals are distinguishable from healthy tissue and demonstrate exactly what we are trying to prove. However, we still do not know whether these discrepancies are the cause or the result of disease. I am currently making progress in research that aims to understand the basic biological features of water by interpreting its behaviors in minute detail.”

Prof. Yasui puts particular emphasis on being able to “see” dynamics of the water within the body.

His team went so far as to join forces with a corporation to make a microscope that could see water. It works by taking a microscopic look at the water as it passes through cells in the body. 3×109 water molecules flow through single aquaporin every second. And 300,000 aquaporins exist in every red blood cell. This indicates that it is vital for water to circulate dynamically throughout the body, but using this microscope Prof. Yasui is able to measure water at its natural speed as it moves through living organisms.

Moreover, recent technological innovations have exponentially shortened the times needed to process and calculate findings, which has allowed researchers to recreate models of the water’s movement using computer graphics.

“When I started my research ten years ago, it could take up to three months to calculate my findings. Now with supercomputers, it only takes three days. We can also now analyze phenomena that take more time. I think that using computer graphics to visually convey our message makes the information much more easily accessible for all types of people,” Prof. Yasui says.

We are finding out that even within the sciences, the life sciences and medicine are particularly complex. Few phenomena can be fully reduced to a single cause alone, and most things are the result of multiple interrelated causes. Prof. Yasui’s research philosophy is to figure out ways of understanding large systems in all of their complexity, he says.

“When you simplify a complex situation, you may lose some of the details. I want to see complex systems for what they are in order to better understand them, however daunting this methodology might seem. When we think about our bodies as a single system, the one thing that holds everything together is water. That’s exactly why I want to learn more about it. The potential to understand the many changing mechanisms of the body is hidden within understanding the key role that water plays,” Prof. Yasui says enthusiastically.

“We have around 20 people at the Department of Pharmacology, but our fields of expertise all differ: agriculture, physics, pharmacy, and mathematics, to name a few,” he says. Prof. Yasui is the only physician. Moreover, the department is unique in the breadth of its research partners, which range from joint research with the Keio University Faculty of Science and Technology to collaborations with corporations in the private sector. Prof. Yasui says he will forgo a single field of research to pursue his visibly ambitious passion for contributing to future health promotion by understanding myriad life phenomena in their entirety.

“As a researcher at the School of Medicine, I would like to see the results of my research have a positive impact on medical diagnosis and the treatment and prevention of disease. Once obtaining biometric information becomes an easy and painless part of everyday life, it will be able to make tremendous contributions to daily health. Numeric data is quantifiable and can be interpreted without having to consult a specialist doctor. This can then be applied to the field of medical education, which still relies in part on intuition.”

As we plunge into an aging society, maintaining good health will become an ever-pressing social issue. There is no doubt of an increasing interest in not only treatment but also prevention, and especially in what we call “offensive prevention.” Taking proactive steps in health management and promotion through early detection will become more and more essential. Prof. Yasui’s research can contribute to this.

“The great Japanese poet Makoto Ooka once wrote a poem in Messages to the Water of My Home. It goes roughly like this:

The earth’s surface is 70% water.
The human body is also 70% water.
Water flows through
Our deepest thoughts and emotions

“As a doctor and as a scientist, these four lines of poetry challenge me each day to build upon and transcend my intuition in my research,” Prof. Yasui says.

Optimistic about the future, Prof. Yasui continues to make progress in his groundbreaking research, together with colleagues in a diverse range of fields and organizations.

Masato Yasui
1989 – Graduated from Keio University School of Medicine (passed national board exam. for medical doctor)
1989 – Clinical Resident of Pediatrics at St. Luke's International Hospital, Tokyo, Japan
1992 – Neonatal Unit Assistant, Maternal & Perinatal Center, Tokyo Women's Medical University.
1993 – Study Abroad in Sweden.
1997 – Completes Doctor of Philosophy (Ph. D.) at the Karolinska Institute in Sweden.
1997 – Postdoctoral Research Fellow at the Department of Biological Chemistry, Johns Hopkins University School of Medicine.
1999 – Instructor at Johns Hopkins School of Medicine, USA
2001 – Assistant Professor at Johns Hopkins School of Medicine, USA
2006 –Full Professor at Keio University Medical Department of Pharmacology

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