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Knowledge Co-Creation - Profiles of researchers

It searches for the principle of the life phenomenon from the biological rhythms.

Hideo Iwasaki
Associate Professor, Faculty of Science and Engineering

Captivated by "Biological Clocks"

While there are probably many reasons why I became a biologist, it may have been because I was born and raised in a family of which many members were scientists, and so had more opportunities to think about questions like "What is science?" and "What is a scientist?" than most people get. Granted, for that very reason I spent quite a while vacillating between going into art (or scientific theory, or history of science in the humanities) and going into science. However, since there were many things about science that I doubted I could conquer through self-study, I advanced into the science department at my university.

I first encountered the concept of "biological clocks," which I've taken as my research subject, when I was in my third year at university. "Biological clocks" are internal, and are said to regulate our sleeping and daily rhythms. The concept first appeared in Germany at the start of the 20th century. If we look back over the process by which it spread throughout the world, we can see that it spread almost simultaneously with a quasi-scientific statement - the German craze for "life rhythms" and US/Japan's 1970s "biorhythm" boom - which was becoming popular around the same time. In other words, as the idea of biorhythms became popular, the concept of biological clocks was used as scientific evidence to support it.

Rhythm is a fusion of both simplicity and dynamics, has both reflexivity and resonance in its nature, and is an apt source for many diverse metaphors. There has been a tradition of metaphorically comparing life to a clock in Europe since the 12th century. My initial idea was that it would be interesting to research this progression as a scientific historian would, but then I thought I should learn more about biological clocks beforehand, and I became a scientist. As a result, I "went for wool and came home shorn," as you can see (Laughs). However, I haven't lost my original interest, and I'm continuing my cultural magazine research on life rhythms as well.

Well, when I actually started doing scientific research on biological clocks, I was startled all over again by just how rich this world really was. This "keeping a rhythm," the foundation of time patterns, exists wherever living creatures do. Since that's the case, research on life rhythms extends over every living species. If you hold a scientific conference on it, mathematicians, medical doctors, and researchers in everything from brains to bacteria to plants will get together and debate on the same topic, and you'll be treated to an extremely rare cross-specialty give-and-take. Captivated by this peculiar interdisciplinary atmosphere as well, I grew absorbed in my research.

Nagoya University's Takao Kondo lab, which I've been affiliated with since graduate school, is currently a world-class research stronghold in the field of biological clock research. When I became a member, though, it had only just started up, and it was the sort of environment where you could do anything you wanted. Just at that time, everyone was working on the hot topic of whether clock genes could be determined or not. I myself was involved in many really fortunate experiences, such as the world's first discovery of and analysis of cyanobacterial clock genes, and discoveries of new biological clock mechanisms far removed from what had been common knowledge for years. These results were published in top science journals such as "Science" magazine and "Cell" magazine, and have been internationally acclaimed.

Professor kondo's lab was also the first in the world to succeed in reconstituting biological clocks inside a test tube. When we mixed the three kinds of clock proteins and energy sources that we'd found inside the test tube, we managed to generate a 24-hour oscillating rhythm. I was right there when it happened, too, but up until a few years ago we'd never have dreamed that it was possible with just three different substances. We'd had the sort of vague idea that "clocks are complicated, so there are probably hundreds of different substances involved," or maybe "we guess rhythm is possible because of those complicated little boxes called cells," and those ideas were completely overturned. It was a truly stirring experience, as though something had poured down upon me from the heavens.

Rhythms of Time and Rhythms of "Shape"

Recently, our research room has been independently developing its research in finding the dynamics in rhythm's spreading from time to space, and in cells' differentiation and morphogenesis. We humans are also just a fertilized egg at first, but that egg differentiates into several different cells, and a being with varied functions and parts is formed. The science of investigating this process is called "embryology".

"Morphogenesis" is the phenomenon of various patterns manifesting along a time axis. In addition, cells that have the same DNA must, while undergoing cell division, differentiate into eye cells, feet cells and all the rest. When two certain conditions (more than two kinds of cell can differentiate from a single kind of cell, and those cells can be maneuvered into their predetermined spatial positions) are combined in an incredibly complicated and clever way, a complex shape such as a human being is created.

We are researching the dynamics of the patterns in this sort of morphogenesis by examining simple organisms like bacteria. Not all bacteria are unicellular organisms; some multi-cellular strains exist. This photograph (Fig. 1) is of a bacterium which has propagated into several strands; a cell different from the others develops at a frequency of about one in ten. Normal cells perform photosynthesis, but these different cells do not; instead they generate the beginnings of amino acids from atmospheric nitrogen and use that for nutrients, while shutting out the oxygen produced by the other cells.

Fig. 1 - A multicellular cyanobacterium which produces a large cell at a ratio of about one in ten. Via a fluorescence microscope (photo below), both the genes involved in pattern formation (green) and activity of photosynthesis (red) are indicated. The large cells have lost their capacity for photosynthesis, and it's possible to see that the genes involved in forming the cells are strongly expressed.

A simple multi-cellular bacterium like this is one of ideal model organism to provide the basic mechanism for morphogenesis and spatial pattern formations. At present, we are investigating exactly how this mechanism is achieved. For example, by lighting up a certain gene using a bioluminescence gene as a reporter, we can observe that it doesn't simply repeat a monotonous luminescente pattern. Instead, as it grows, it begins to develop a bias to the light in a certain rhythm, and that one odd cell in ten is formed. We hope that, now that we've illuminated this simple principle, it may be more broadly applied and help explain other phenomena.

As an easily understandable example of spatial distribution rhythm, take the Wave (the spectators perform at soccer games). The Wave is created when the spectators, one by one, raise their arms in a staggered rhythmic phase. Again, when someone making soba noodles cuts the soba evenly at set intervals, that's a spatial rhythm. It's a combination of the act of gripping a kitchen knife and going "tunk-tunk-tunk" against the cutting board at a regular speed, and of moving the wooden board with the lump of soba dough on it at a regular and precise speed. Actually, the mechanism of the regular interval pattern that forms the spine closely resembles the rhythm of cutting soba. Hints to the dynamism of life's phenomena are hidden in familiar phenomena like this.

In the process of researching these biological phenomena, we sometimes intentionally upset (or perturb) the rhythm. By observing the resulting disorder, we try to pin down just what's happening. For example, going back to the soba cutting, if we don't change the speed at which the cutting board is moved but decrease the cutting rhythm by half, the noodles come out wider, right? Deepening one's knowledge by changing something by a little, then watching to see how the pattern changes, is a very common method.

Towards a Biology That Understands as it Creates

When your research enters the "micro" world, micro-devices which can manipulate minute things become important. Going back to the previous example, through obtaining new tools (such as a tool which disrupts a pattern, or a tool which can incubate bacteria under a microscope for long periods of time), previously impossible research becomes possible. Our school's electric and bioinformatics major is a truly interdisciplinary major consisting of science and engineering; as a result, there are many in engineering who are particularly good at making micro-devices, and we've already begun teaming up for cooperative research. I look forward to seeing what new discoveries we'll gain from it.

We're also being careful to use an approach of "understanding as we create." In the building world, we have an idea and a blueprint of the thing we want to make, and we piece its components together to create our ideal complete object. In contrast, in biology, it's been customary to have a live "complete object" right in front of us, dismantle it into fine pieces, and then research the parts, but it was always difficult to plot out the blueprint by which the whole thing worked. Still, as you'd expect, biology's highest aim is to plot out these blueprints held in living things and biological phenomena. Once we get those blueprints drawn up, we next have to make something by using to them, watch how things go to see whether we've drawn them correctly or not, and then confirm that the phenomenon can be recreated. This inspection work and system design testing is what's known as the "synthetic biology" approach. (Fig.2)

Fig. 2 The approach of synthetic biology is to combine the upwards flow (red arrow) of conventional biology and the biological sciences with the downwards flow (green arrow) of engineering, making the blueprints for biological phenomena clear in the process.

I think that research which consists of drawing up a new blueprint based on one's own discovery, putting together the "wet" biological ingredients such as proteins and genes, and producing a biological phenomenon previously nonexistent in the world of conventional biology will probably become one of the mainstreams of biology in the future. Studying both biology and electric/electron engineering at the same time and conditioning oneself to an approach combining science and engineering will be terrifically effective in the synthetic biology of tomorrow.

However, when it comes to creating a biological phenomenon or going one step further and artificially creating cells, depending on the situation, it becomes important to consider bioethics or the cultural view of life on a wider scale. It will be necessary to set up system whereby we take into account the vague unease that people hold, thoroughly map out where problems in ethics or safety lie, present the research positively to society, and respond to society's doubts. At the same time, such ventures will achieve nothing less than beginning a dialogue on biology between ourselves and society and those in other fields, thus deepening everyone's understanding of the subject. That itself could be called one of the riches that synthetic biology holds. For that reason, my research companions and I started a research society on "creating cells" last year as a place to discuss synthetic biology, exchange information and publicize research, not just with scientists and technicians, but with those in the humanities and sociology fields as well. Among those, it's my responsibility to care for the unit that deals with the societal and cultural facets.

Instead of just discussing risk and safety, we try to grasp the varying ways of looking at biology from an ever-widening perspective. In order to deepen understanding, we advocate open exchange with those in the humanities, sociology and the arts even at the research room level; we hold open research summits, inviting attendees from both inside and outside the university, and advocate cooperative research. In the art world, for example, there are already several works dealing with biomaterials, and these can be terrific stimulation for the biologist. Therefore, this year we've begun a very exciting trial, deciding to permanently station artists in my research room and see what sort of new things they come up with. In the near future, I'd like to open a gallery for the results and give lots of people the opportunity to come and view them.

Scientific logic alone can't provide the answer as far as science's dealings with society and culture are concerned. Scientists often say a topic is "scientifically interesting," but that expression "interesting" itself is very "human" and "cultural," don't you think? At first glance, science seems to be objective, but it may be shored up by all things cultural, historical and idealistic, or it may be illogically passionate. Keeping in mind the fact that science is always being influenced by the political, cultural and ethical perspectives that form the backdrop of the age is, for a scientist, both important as far as "knowing thyself" is concerned, and enjoyable.

Hideo Iwasaki
Associate Professor, Faculty of Science and Engineering, Waseda University (Department of Electrical Engineering and Bioscience)

Hideo Iwasaki is a professor (Science), having completing his research in the biology department of Nagoya University Graduate School. He has been employed since 2005, after experience as a Research Associate of the Japanese Society for Promotion of Science and as an professor at Nagoya University. Since 2007, he has also been employed as a "PREST" researcher from the Japan Science and Technology Agency (JST) . Making the best use of molecular biology and mathematical scientific analysis, etc., he has turned his hand to researching the spatio-temporal pattern formation dynamics of bacteria and, having proposed such things as the identification of clock genes and new oscillation models, is carrying out cultural magazine research dealing with biologoca; rhythms and artificial cells. He has been the recipient of the Japanese Society for Chronobiology Prize (2003), the Inoue Prize for Young Scientists (2001), and the 2008 Ministry of Education Science Minister Commendation Young Scientist Prize. Also currently active as a cut-paper artist, he received the Toyota Triennale Outstanding Award (3-D Art, 2004) and the Howard Lichter Prize (Spiral Independent Creators Festival, 2008).
(Homepage: http://www.f.waseda.jp/hideo-iwasaki/)

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