情報：農と環境と医療48号

I would like to offer a few opening remarks on behalf of the sponsor of this Sixth Kitasato University Agromedicine Symposium.

There is no way to overemphasize the need for agromedical science and education in fields such as disease prevention, health improvement, safe food, conservation agriculture, and healing agriculture; in other words, for the health and safety of people living in the 21st century.

This agromedicine symposium presented by instructors at Kitasato University, who are explorers of the life sciences, is titled "Food Safety and Preventive Medicine".　

The situation surrounding dietary lifestyle and preventive medicine has undergone sizable changes. These include globalization of food, the appearance of new hazards such as Escherichia coli O157 and misfolded prion proteins, the development of new technologies such as genetic recombination, and poisoning incidents typified by Chinese-manufactured foods. It has been some time since scientific information on food safety and preventive medicine started making its way deeply into our everyday lives.　

The consequence is a trend that obliges us to have a constant consciousness of science at the dinner table. The anti-oxidant effect of red wine's polyphenols is emphasized, while nothing is said about the problem of what increased alcohol consumption does to health. You are conscious of avian flu just eating one stick of grilled chicken. And when you look at the packaging of gyoza, you wonder where they were made.　

Another trend now is to emphasize the efficacy and impacts of the constituent parts of a food, while saying nothing about what happens when they are put together. One type of knowledge is isolated from another.　

Because foods are an amalgam of many constituents including carbohydrates, fats, proteins, minerals, and vitamins, they have both upsides and downsides. Since ancient times we have had great concern for taste and preservation methods to keep a delicious, well-balanced diet. Everyone knew that when foods have no additives, they spoil and increase the risk of food poisoning.　

Through our long human history, people have gained the wisdom to eat a balanced diet of various foods. It seems that modern food and preventive medicine with their underpinning of science and technology are making us forget our human history, practices, and common sense.　

The latest food safety and preventive medicine are sustained by drawing on the latest science and technology. My hope is that this symposium will consider, from the standpoints of agricultural science and medical science, how this food safety and preventive medicine can collaborate.　

In closing, I would like to express my sincere gratitude to the speakers who gladly agreed to address this symposium.

1.Introduction

The Food Safety Commission was established in July 2003 as an "organization to objectively, neutrally, and impartially assess food safety based on science". This July it was five years old. Today I will review the commission's initiatives over the first five years and outline its future challenges.

2.Creation and Role of the Food Safety Commission

1) Contexts of the Commission's Establishment

The circumstances surrounding our dietary lives have undergone considerable changes, including the advancing geographical broadening and internationalization of food distribution, the appearance of new hazards such as O157 and abnormal prions, the development of genetic recombination and other new technologies, and improvements in analysis techniques.
Meanwhile, a new approach to food safety is a risk analysis method that has become generally adopted internationally. In this approach, all foods should be scientifically assessed and controlled under the assumption that they present risks. Risk analysis methods comprise the three elements of risk assessment, risk management, and risk communication. Risk assessment involves scientifically assessing the health impacts of ingesting hazards in food. Risk management is carried out, based on risk assessment results, for purposes such as deciding pesticide residue and usage of standards, and pesticide regulation, while taking into consideration of cost-effectiveness, technological possibilities, and popular sentiment. There is also supposed to be risk communication, involving the exchange of views and information, through risk assessment and risk management with involved parties including consumers and food businesses.

2) Creation and Role of the Food Safety Commission

Under these circumstances described above, Japan's first case of BSE surfaced in 2001, which elicited scathing criticism of the government's response from the citizens. Based on a sense of remorse over food safety administration until that time, in July 2003, the Food Safety Basic Law entered into force and the Food Safety Commission was established under the Cabinet Office.
The purpose is to incorporate risk analysis methods into food safety administration and to perform food safety-related risk assessment independently of the Ministry of Agriculture, Forestry and Fisheries (MAFF) and the Ministry of Health, Labour and Welfare (MHLW), while according the highest priority to protecting citizens' health.
In addition to risk assessment, the commission carries out risk communication, and in the event of a mass food poisoning incident, it is responsible for gathering information, informing the citizenry, and taking other emergency actions to respond.
The Food Safety Commission is composed of seven commissioners, and has 14 expert committees. The "Planning", "Emergency Response", and "Risk Communication" committees deal with crosscutting issues, and the remaining 11 expert committees study and discuss risk assessment for individual hazards such as additives, pesticides, veterinary medicines, microorganisms/viruses, prions, and genetically modified foods.

3. Initiative and Achievements over the First Five Years
1) Initiatives over the First Five Years

Risk Assessment
 
The Food Safety Commission's most important role is risk assessment. In response to requests from the MHLW and the MAFF, which are risk management organizations, the commission conducted over 600 risk assessments in this five-year period. The commission also conducts "self-initiated assessments", which are risk assessments on subjects chosen by the commission at its own discretion.　
Assessments on BSE are important assessments that test the true value of the commission. The commission collected information and data widely in Japan and other countries, conducted careful scientific discussions, and performed risk assessments including "Medium-Term Summary of Measures to Address BSE", "A Review of Japan's Measures to Address BSE", and "A Risk Assessment of Beef and Other Products Originating in the United States and Canada."
In addition to BSE, the commission carries out risk assessments on Campylobacter jejuni, C. coli,and other microorganisms that cause food poisoning, and on drug-resistant bacteria that are selected for by the use of antibiotics on livestock and other animals.
Furthermore, in conjunction with the introduction of the "positive list system" in May 2006, the commission is performing a series of assessments on 758 substances including pesticides and veterinary medicines.

Risk Communication
 
The Food Safety Commission endeavors to use every opportunity and communication tool to carry out risk communication, including opinion exchange forums held around the nation and by seeking opinions and information on such things as risk assessment results, as well as by releasing information on the web and providing information through various media including printed materials and DVDs. In our first five years, we held 324 opinion exchange forums, and sought opinions and information for 353 times.
Starting in 2006, the commission has been cooperating with municipalities by holding regional leader training courses to foster people who will actively facilitate risk communication in outlying regions.


What is more, in order to avert social turmoil or excessive concerns among the populace, the commission takes advantage of its nature as an organization conducting scientific risk assessments to release media statements from the chair of the commission on matters vitally related to health damage from eating food, such as with avian flu.

2) Five Years' Achievements

Since July 2003, the Food Safety Commission has performed risk assessments objectively, neutrally, and impartially as an independent organization conducting science-based deliberations, while maintaining a relationship with risk management organizations in a collaborative but restraint manner. Our five years' effort for the initiatives seems to be paying off, because the idea of risk analysis has found a home among those who are involved in food safety.
In addition, owing to the creation of the commission, works such as in laying the foundation of risk communication, to secure as in securing transparency in the risk assessment process by releasing the deliberation process, and regularly using tools such as opinion exchange forums and seeking opinions and information. We have also strengthened our provision of food safety information to the public.

4. Future Challenges Facing the Commission

Upon the five-year milestone of the Food Safety Commission, we must summarize our five years of accomplishments and review our operations. The need for the reform of the Food Safety Commission has also been pointed out in discussions by the Consumer Affairs Administration Promotion Council and other venues during the creation of a Consumer Affairs Agency.
Bearing in mind the attention and expectation of the parties concerned, the commission intends to work on the challenges detailed below to further strengthen its functions and role.

1) Risk Assessment

In the area of risk assessment, the commission has responded to the increasing number of cases to be discussed, and has made improvements including reviews of its deliberation system and methods among others. Nevertheless, many cases remain to be assessed. Many more assessments are expected due to the factors such as the positive list system and the development of new technologies. Therefore, it is necessary to conduct risk assessment deliberations more effectively and efficiently.　
Some reputations on the self-initiated assessments are that "there are only few cases" and "the commission should assess more generally concerned cases by consumers". To satisfy those views, the selection process for the items of self-initiated assessment needs to be re-examined. Additionally, tasking self-initiated assessments will require furthermore data/information correction. The data analysis system also will need to be reinforced.

2) Risk Communication

Some reputations on risk communication are that "assessment results are hard to understand" and "the mutual flow of information and opinions is not assured". In addition, municipalities have various degrees of commitment to risk communication initiatives, and efforts to foster people to sustain risk communication in outlying regions have just begun.　
In view of this situation, it is necessary to make changes. Preparing materials on risk communication in more easily understandable manner, reforming opinion exchange forums and other gatherings for more participation, and improving the way the opinions and information are sought. It will also be necessary to support the autonomous initiatives of the municipalities, and to facilitate the commission's collaboration with them.　

3) Information Provision

In the area of information provision, it is doubtful if there is broad and sufficient understanding among the public about the risk analysis approach introduced by the Food Safety Basic Law. Same goes to the roles, activities, and other aspects of the Food Safety Commission. At a time when food-related problems are arising, there is a need for information provision that will moderate the public concerns about food safety.
This creates a need to make active use of diverse media and means for the provision of more easily understandable about risk assessment framework and the role of the Food Safety Commission. Another challenge is how to make the timely release of chairperson's media statements and other information when potentially alarming food safety problems arise for the public.

4) Internationalization of Commission Activities and International Linkages

In the age of food globalization, it is important that not only Japan actively participates in creating international standards, but also that consistency of domestic Japanese standards with international standards. Due to having introduced the changes such as the positive list system, there is a sharp increase in the number of cases demanding attention to international trends in relation to risk assessment.
In view of these circumstances, it is essential to quickly obtain information on risk assessment results and assessment methods in other countries, and to cooperate in the work of international risk assessment. The Food Safety Commission will need to strive on strengthening collaboration with international agencies and organizations of other countries. In particular, the commission intends to bolster its collaboration with the European Food Safety Authority (EFSA) such as through the exchange and sharing of everyday information.

5. Conclusion

As of the 248th meeting on July 24, 2008, the Food Safety Commission considers its way of improvement. In view of the necessary steps ahead, the commission plans to hold discussions and produce a final summary of improvement measures before the end of FY2008.

Introduction

One major problem in the world now is the "disjunction disease". We see it in the bonds between people, between parent and child, between teachers and students, between soil/nature and humans, between one fact and another, between culture/history and the present, and in countless other examples.　
Looking through the examples shows there are four types. The "disjunction of knowledge from knowledge", examples of which are immersion in specialization, the maze of specialized terminology, and the use of non-alive language. The "disjunction of knowledge and action", examples of which are the disjunction between those who construct theories and those who are responsible for practice, and the disjunction between the virtual and the real. The "disjunction between knowledge and feeling", that is, thoroughgoing objectivism, and the extreme disjunction between knowledge and reality. The "disjunction between past knowledge and present knowledge," that is, the disjunction of the time axis where we learn from history and the passing on of culture, as indicated by terms such as "finding eternal truths in popular trends" and "learning from the past."
At the start of On the Way of Medicine(1878) author Shibasaburo Kitasato(1853～931) states his conviction about the healing art. It includes this passage: "The foundation of the way of medicine is to lead the people, have them understand how to care for and protect their health, and with this, to inform them of the value of their physical selves, and hence provide them with the way to prevent illness." To paraphrase this, he is saying, "The basis of medicine is to explain to the people how to maintain their health, tell them about the importance of their bodies, and prevent illness." Another interpretation of this is that it is necessary to eat food that has been produced in a sound environment and produced in safe manufacturing processes, maintain one's health, and not fall victim to illness. Truly, that is the title of this symposium, "Food Safety and Preventive Medicine".
Kitasato continued with scathing criticism of the physicians of his day, which can be paraphrased in this way: "Preventing illness cannot be achieved without a full understanding of medicine; that is, what causes illness and how to cure it. To provide true medical care, one must fully research the healing art. Those who aspire to medical science must exhaustively research both theory and technique, without more weight on one or the other." Another possible interpretation is that before seeing a doctor, people should produce safe agricultural products that prevent illness, and conserve the underpinning environment.
To briefly sum up Shibasaburo Kitasato's On the Way of Medicine, he sets forth the conviction that the foundation of medicine is prevention, and says that the achievements of academic inquiry should be used widely to benefit the people. Here we see the idea of practical science that links academic inquiry with practice. There is no disjunction between knowledge and knowledge, or knowledge and practice.
On a trip to Nagasaki for a cholera study, Kitasato used his free time to accurately observe the state of roads, wells, drainage, and other elements of the environment in back streets where people had fallen ill. In relation to liver distomiasis, which is caused by a parasite, he describes the route by which the liver fluke (a flatworm 20-30 mm long, belonging to the order Echinostomida (digeneans)) infects the liver. This achievement was due to his sharp-eyed observations of the environment. He urges attention be directed at sheep that eat the snails that harbor flukes. This is indeed the practical science of Shibasaburo Kitasato, who linked academic inquiry with the real world.
Incidentally, On the Way of Medicineconcludes with a Chinese-style poem with seven-character lines. The meaning can perhaps be summed up in this way: "If a man endures and braves hardship, there is no reason to expect that he cannot successfully surmount the challenges of public health".
Shibasaburo Kitasato's practical science naturally did not include the disjunction disease. In fact, we must learn from Kitasato's foresight. Agriculture, the environment, and medicine should never have been separated.
With respect to agriculture, the environment, and medicine (that is, agromedicine in an environmental context), who will represent us in examining the desirable state of inter-regional connections within single countries, international connections in the world, interdisciplinary connections among specialties, and intergenerational connections between now and the future? The answer is that those on the forefront are the intellectuals.
But in the near-modern and modern eras, intellectuals are on the decline. In their place there is a growing number of experts who are proficient in certain fields, and that trend is further accelerating amid the advance of our highly information-oriented society. There are few people who give knowledge an integrated interpretation, while those who partially interpret knowledge and use it shrewdly have begun to swagger. What is more, many experts appear to be immersed in their specialties in order to avoid the responsibilities of their fields. The problem of agromedicine in an environmental context is that it is an extremely difficult field for being an intellectual. How should we deal with this situation?
Chapter 11 of the Chinese classic Dao De Jingby the "Tao" philosopher Laozi contains this passage.

• "We put thirty spokes together and call it a wheel;
• But it is on the space where there is nothing that the usefulness of the wheel depends.
• But it is on the space where there is nothing that the usefulness of the vessel depends.
• We turn clay to make a vessel;
• We pierce doors and windows to make a house;
• And it is on these spaces where there is nothing that the usefulness of the house depends.
• Therefore just as we take advantage of what is, we should recognize the usefulness of what is not. (chap. 11, tr. Waley)"

(Arthur Waley, The Way and Its Power: A Study of the Tao Te Ching and its Place in Chinese Thought, London, Allen & Unwin, 1934, New York, Grove, 1958.)　

Here is thought which shows a fundamental principle for unifying diversity. If we interpret this text from the stance of agromedicine, it would mean that to bring about the functions of an "agriculture-environment-medicine" or "food-soil-health" collaboration, it is necessary to use information, education, research, dissemination, and other things each as a useful material in building new rooms.　


To aid the search for what agromedicine should be in the future, I shall build on the thinking presented above in describing the state of progress achieved at Kitasato University so far in education, information, research, dissemination, and other agromedicine-related areas.

1. Publication of "Information: Agriculture, Environment, and Medicine"

To promote broad awareness of agromedicine-related information among parties concerned, the university has been sending out "Information: Agriculture, Environment, and Medicine" as a newsletter from the office of the president of Kitasato University. It has been published on the first of every month since the first issue in May 2005, with the 46ｔｈ and most recent issue in January 2009. Newsletter sections include "Opening Remarks", "University Happenings", "Domestic Information", "International Information", "General Remarks, Resources, and Topics", "Laboratory Visits", "Useful Literature", "Books and Resources", "Lecture Presentations", "People with Agromedicine at Heart", "A Stroll Through Words", "Agromedicine", "Geomedicine", and "Miscellaneous".
Windows, and doors spoken of by Laozi indicate distinctiveness or individuality, while the wheel, vessel, and room indicate the unification of diversity. For example, among the sections of "Information: Agriculture, Environment, and Medicine", the "International Information", "Domestic Information", "Books and Resources", "People with Agromedicine at Heart", and "Faculty Visits" sections correspond to the clay and window. The wheel, vessel, and room have yet to be made. A room called "agromedicine" will of course not suddenly appear or be built.
The agromedicine "room" will only be built after a long time with the interest, cooperation, assistance, effort, and other involvement by many people. If the room is built, though it be a humble one, we can put curtains in the windows, hang paintings, and bring in desks and chairs. In time, we will even get a big sofa for visitors.

2. Holding the Kitasato University Agromedicine Symposiums

In addition to "Information: Agriculture, Environment, and Medicine," there is another effort to unify the diversity of agromedicine, and that is the Kitasato University Agromedicine Symposiums. The first was held in March 2006, and we have hosted them at a pace of one every six months. This October 2008 symposium is the sixth. These symposiums perhaps correspond to the door of the agromedicine room.　

3. Holding Medicinal Plant Seminars

With the intent of creating a new urban agriculture, Kitasato University and Sagamihara City have signed an "Agreement on Encouraging a New Urban Agriculture", and are running a collaborative project that involves medicinal plants. As an integral part of this initiative, the partners are working on promoting public awareness of medicinal plants and their use. Additionally, in an effort to heighten interest in new agriculture and to encourage a new agriculture whose focus is on health, the environment, and new urban agriculture, the partners have to date held three "Medicinal Plant Seminars" as an integral part of the liaison between agriculture and medicine.　

4. Education: Holding Lectures on Agromedical Theory Reports

Starting with the students who matriculated in April 2007, lectures on agromedicine account for part of the "Theory of Medical Science" lectures for first-year medical school students, and part of three courses for first-year veterinary medicine students: "Introduction to Veterinary Medicine I," "Outline of Animal Science I," and "Outline of Environmental Bioscience I."
In April 2008, we added the course "Agromedical Theory" (one credit) to the College of Liberal Arts and Sciences' "Liberal Arts Seminar B". Professors including those from the School of Medicine, School of Veterinary Medicine, School of Pharmacy, and the Kitasato Institute for Life Sciences take turns delivering lectures.
Under the "High-Quality University Education Promotion Program", we have applied for a project called "Aiming to Build Career Paths Leading to High-Level Professionals through Mastering Composite Knowledge and Technologies".　

Content of "Liberal Arts Seminar B:
Agromedical Theory" in the College of Liberal Arts and Sciences

1) Education objective

For purposes including illness prevention, health improvement, safe food, conservation agriculture, and healing agriculture, in other words, for the purpose of making people living in the 21st century happy in both body and mind, it would be impossible to overemphasize the need for agromedical science and education. It is vital that Kitasato University students, who are explorers of the life sciences, are aware of the importance of agromedicine. In this seminar, students learn basic ways of thinking such as the historical similarity between agriculture and medicine, the agriculture- and medicine-related problems in modern society, agricultural science as seen from medical science, and medical science as seen from agricultural science. The objective is to have students understand real-world phenomena relating to agriculture and medicine in an environmental context, and to learn the necessity of agromedical science.

2) Education content:

Students acquire basic knowledge from courses such as Introduction to Agromedicine, Agromedicine as Seen from the Medical and Agricultural Sciences, Alternative Medicine, and Alternative Agriculture. They also acquire specific global-scale knowledge on avian flu, heavy metal elements, and global warming and agriculture/environment/health. Courses explain the state of agromedical initiatives around the world. There is discussion and examination of the future of agromedicine.

3) Education method

Lectures and seminars by instructors from various schools and practicing professionals. Lectures use means such as PowerPoint presentations. Students write reports on and discuss lecture series. In final sessions, participants discuss and examine the preferable future of agromedicine.

4) Goals

Students can understand that in the 21st century the science of agromedicine is essential. They can understand the historical backgrounds of agriculture and medicine. They can see world agromedical trends and see the actual state of agromedical practice.

5) Grading method and criteria

Reports, tests, attendance, active participation in discussions, and other factors are taken into consideration, and an overall judgment is made.

6) Message to students

Efforts to solve the problem of how we can link the objectives of medical science in the 21st century with the challenges of agricultural science not only respond to the demands of society but also are vital to Kitasato University, which aspires to be an explorer of the life sciences, and to those who study at Kitasato University.

7) Content of lectures

1. Introduction to Agromedicine: Katsuyuki Minami
   This lecture explains the need for agromedical science while pointing out the historical similarity between agriculture and medicine, and the problems of agriculture and medicine in modern society, and conducts an exchange of views about this.
2. Agromedicine as Seen from Medical Science: Yoshiharu Aizawa
   To lead a healthy life in a society that aims to become sustainable, it is crucial to implement nutritional education and nutritional science. The importance of agromedicine is explained along with the lecturer's personal experiences.
3. Agromedicine as Seen from Agricultural Science: Katsuyuki Minami
   Food that is capable of maintaining human health can be produced only from soil that has a good balance of nutrients. This lecture introduces the idea that medicine and food spring from the same source, has students understand the need for agromedical science and education, and has them discuss the importance of food.
4. Agromedicine as Seen from Oriental Medicine and Alternative Medicine: Haruki Yamada
   This lecture explains Oriental medicine, the official medicine of Japan, while comparing it with Western medicine and recent alternative medicine, and expounds on the current state of and need for agromedicine.
5. Alternative Agriculture: Katsuyuki Minami
   Conventional agriculture uses large amounts of pesticides and chemical fertilizers. This has adversely affected crops and the environment. This lecture introduces students to various substitute agricultural practices, explains the need for alternative agriculture, and has students see it in action.
6. Conservation Livestock Farming ?From Production to the Hospital Ward: Tomiharu Manda
   This lecture introduces students to conservation livestock farming, and describes a system which safe animal products produced in well-conserved environments are used advantageously in hospital wards. The initiatives at Yakumo Farm are also described.
7. Avian Flu ?Infection and Control Measures: Shinji Takai
   This lecture explains that infection of animals and humans by bird flu is intimately connected to the natural environment and to agricultural production sites, describes how infection happens in the real world, and considers control measures.
8. Avian Flu ?Vaccine Measures: Tetsuo Nakayama
   This lecture explains ways to prevent infection of people with bird flu, how vaccines are manufactured and used, and other related information.
9. Heavy Metals ?A Biogeoscience Perspective and Dealing with the Risk of Soil and Agricultural Product Contamination: Katsuyuki Minami
   This lecture explains from a biogeoscience perspective the amounts of heavy metals extracted from the earth's crust and their behavior in the environment, and provides other information such as the processes by which heavy metals are absorbed by the soil and crops, and control measures.
10. Heavy Metals ?The Perspective of Clinical Ecology: Kou Sakabe
    Health damage caused by heavy metals is a very serious problem in the field of clinical medicine. This lecture explains the history of heavy metals and people, onset mechanisms, and more.
11. Global Warming and Agriculture, the Environment, and Health: Katsuyuki Minami
    It is said that global warming is advancing much faster than experts had anticipated. What will happen to agriculture, the environment, and human health because of global warming? The most recent data is used to give the students an understanding of global warming's seriousness, and discusses how to cope.
12. Initiatives and Future of Agromedicine: Katsuyuki Minami
    This lecture introduces students to agromedicine initiatives in North America, the Nordic countries, Japan, and other places around the world. This lecture explains concepts such as agromedicine and medical geology. This lecture encourages an exchange of views on matters such as how agromedical science and education should be developed.

5. Kitasato University Symbiosis Research: Research Laboratories and Research Agenda

In the quest for research materials and people capable of linking agriculture, the environment, and medicine, we explored a variety of research departments, starting in April 2005 with Hygienics and Public Health in the School of Medicine and ending in July 2007 with Veterinary Infectious Diseases in the School of Veterinary Medicine. Issues 1 through 28 of "Information: Agriculture, Environment, and Medicine" have information on the 26 courses and research departments of Kitasato University that we visited, including descriptions of the research.

Food is essential for maintaining human life. Since ancient times we have had the dietary habit of preparing ingredients and eating food together. Everyone wants to have sound dietary habits and lead a healthy life. In other words, food has roles that are important both as the foundation of daily life and medically, such as by maintaining health, improving the quality of life, and preventing and curing illness. At the same time, many issues have arisen with respect to the safety and functionality of food, and concerns about ingredients and foodstuffs are now much greater than in the past. Dietary lifestyle is said to include: (1) maintaining our physical health, (2) maintaining our mental health, (3) maintaining social health, (4) passing on culinary culture to future generations, and (5) education. By means of eating, we have used these functions to maintain life.

But in postwar Japan, with its scientific and technological development and economic growth, our dietary lifestyle has transitioned into gourmet pursuits, instant food, and "healthful" eating. For this reason, lifestyle diseases such as diabetes and metabolic syndrome are now of great significance, while the linkage of health maintenance, good taste, and safety is important to the dietary lifestyle of Japan because of its high median age.　

More and more people now subscribe to the thinking that to prevent lifestyle diseases, even if one falls victim to metabolic syndrome or diabetes, we should to the greatest extent possible avoid medicine and cure and prevent illness by managing our own health with food and exercise. Owing to this state of the modern dietary lifestyle, there are high expectations for the expertise of registered dietitians, whose job is to prevent and cure illness with food. Registered dietitians appeared with the partial revision of the Dietitian Law in 1962, wherein they were defined as people who provide the complex, difficult nutritional guidance that ordinary dietitians cannot do. A 2000 revision of the Dietitian Law defined registered dietitians thus: "The title of registered dietitian is conferred when licensing by the MHLW to people whose occupation is: to provide nutritional guidance necessary for the medical treatment of the sick and injured; to provide nutritional guidance for the maintenance and improvement of health requiring advanced specialized knowledge and techniques corresponding to the physical condition, nutritional condition, and other attributes of individuals; and to manage the preparation of meals requiring special consideration for the physical condition, nutritional condition, type of use, and other attributes of people using facilities which provide meals on a continuing basis for large numbers of specific people, as well as to provide guidance and other assistance needed to improve nutrition in such facilities."

Dietetics, which is the specialized and academic foundation of registered dietitians, is made up of three elements: the human body and health; food and nutrients; and food-related behavior and the social environment. In other words, dietetics is an academic system comprising the fields of medical science, agricultural science, and home economics. Registered dietitians are involved in research and education on the functionality of the various constituents of foodstuffs, education on primary prevention by improving dietary habits (nutritional education), secondary prevention (such as specific medical checkups and health guidance for metabolic syndrome), and welfare as tertiary prevention (facilities for the elderly). Registered dietitians are also involved in education for knowledge and techniques for bedside nutritional management in the treatment of disease (for members of nutritional support teams in team medical treatment). Here we describe two examples of our efforts to link agriculture and medicine in the context of Current Dietary Lifestyle and Its Challenges: Linking Health Maintenance, Good Taste, and Safety.

Nutritional State of the Citizens: Results of National Health and Nutrition Survey

In recent years, because of the increase in lifestyle diseases, obesity, and the like, attention has been focused on nutritional problems. Further, in April 2008 the government started providing specific medical checkups and health guidance for all citizens 40 years or older, and nutrition for health improvement is considered important. According to the results of the 2006 National Health and Nutrition Survey, there were 5 million more people with a lifestyle disease (diabetes) than four years before, and among people aged 40 to 74, one in two men and one in five women were strongly suspected of having metabolic syndrome or getting it in the future. There were more obese men in all age groups than 20 and 10 years before. In particular, 30% of men aged 30 to 60 were obese. In terms of nutrient intake, there was a gradual trend toward ingesting less energy. However, there was also a gradual increase (about 20% of men and 30% of women 20 years and older) in the number of people who ate less carbohydrates and derived 30% or more of their energy from fat. With regard to dietary habits, the higher percentage of people who skip breakfast and the trend toward later dinner times suggest the need for improved dietary habits.

Nutritional Characteristics of Yakumo Beef

Kitasato Yakumo cattle yield safe, worry-free Healthy Beef because they are 100% raised on farm-grown pasture on which no chemical fertilizers have been used at all. Nutritionally the beef is superior to that of conventionally fattened cattle and is characterized by constituents having more tertiary functions such as anticancer action and arteriosclerosis prevention. In particular, the fatty acid composition is lower than that of marbled beef, with a ratio of n-6 to n-3 fatty acids around the appropriate value of 4. Kitasato Yakumo Healthy Beef has a high concentration of conjugated linoleic acid (for which various physiological functions such as obesity prevention, improved fat metabolism, and improved insulin resistance are reported), at about twice that of conventional beef. What is more, Kitasato Yakumo Healthy Beef contains high levels of iron (which when deficient will lead to anemia), zinc (which when insufficient leads to gustatory disorders and lowered immunity), and magnesium (which plays an important role in energy metabolism). Therefore, it is a food nutritionally appropriate for preventing lifestyle diseases.　

Initiatives by the Kitasato Junior College of Health and Hygienic Sciences' Applied Clinical Dietetics Department

This academic year the college launched a project to develop processed foods and recipes for hospital meals using Kitasato Yakumo Healthy Beef. We tackled the development of cuisine that takes advantage of the meat's nutritional characteristics and flavor as an integral part of education. In a sensory test involving students, many subjects said that although Healthy Beef was inferior to Aussie Beef in terms of tenderness and smell, its appearance (color) and taste was superior. We offered curry with our beef to patrons at a lunch during the college PPA meeting, and only 17% of them said the beef was tough. For that reason we have classes in which students think about cooking methods which take advantage of the characteristic firmness and flavor, and produce delicious cuisine.
Henceforth we intend to take advantage of the meat's nutritive and sensory characteristics, and from the perspective of preventing lifestyle diseases, practice the development of processed foods and hospital meals using Yakumo Healthy Beef.

Introduction

Dietary fiber used be considered worthless in terms of nutrition, but now it is spotlighted as the "sixth nutrient" along with proteins, fats, sugars, vitamins, and minerals, and is seen as useful in preventing colon cancer and lifestyle diseases.
Although dietary fiber has long existed, it has a short research history, and it is still a poorly understood field. However, preventive medicine has big expectations for the direct and indirect bioactivity of dietary fiber.
Here I report the latest findings on the definition and classification of dietary fiber, and the relationship of its bioactivity to health. Additionally, I report on the possibilities and food applications of resistant starch, which has an especially unusual function.

Dietary Fiber Classification and Definition

The types of dietary fiber include soluble, insoluble, plant, animal, bacterial, natural, artificial, and chemically modified. In Japan, the definition of dietary fiber is "a general term for indigestible constituents of food that are not digested by human digestive enzymes". The Japanese Association for Dietary Fiber Research proposes the word "lumiconide" as a blanket term for substances, including dietary fiber, which are indigestible, unabsorbable, and have some kind of physical action in the digestive tract. Their definition is "a food constituent that is difficult to digest or absorb in the human small intestine, and manifests a physiological effect via the digestive tract that is useful in maintaining health".

Dietary Fiber Bioactivity

From the experimental, clinical, and epidemiological verification results to date, it is known that dietary fiber manifests a variety of physiological effects in the process of passing through the digestive tract. Some representative physiological effects are that fiber effectively regulates the intestinal environment, facilitates bowel movements, and prevents colon cancer; it is also effective for preventing lifestyle diseases such as diabetes, hyperlipidemia, hypertension, and obesity.
In addition to being generally low energy, dietary fiber is fermented by intestinal bacteria in the colon resulting in the formation of short-chain fatty acids. These short-chain fatty acids facilitate the proliferation of colonic epithelial cells and suppress the synthesis of cholesterol, which offers promise of a new effect that was previously unknown.

Application of Resistant Starch in Foods

Resistant starch is defined as "a general term for starch and partially water-soluble starch that is not digested or absorbed in the small intestine of a healthy person". There are four types of resistant starch categorized from RS1 to RS4.
A feature of resistant starches is that they combine the properties of both soluble and insoluble dietary fiber, and are known to have various beneficial effects including improving bowel movements, mitigating colon disorders, lowering blood cholesterol, improving blood sugar level, improving mineral utilization, and producing short-chain fatty acids from fermentation by colonic bacteria.
Resistant starch is also excellent for food processing. For example, it can be added to starchy foods such as bread, noodles, pizza, and other staples. An advantage is that it can be added in large quantities without impairing texture, flavor, or aroma. Thus, one can continuously consume it naturally from daily meals. Presumably using resistant starch effectively makes it possible through ordinary meals to improve one's intestinal environment and prevent lifestyle diseases.

1. Fisheries Industry Target Species

The oceans and the rest of the hydrosphere are populated by a vast diversity said to comprise 500,000 or even 5 million species from plankton to cetaceans. Of those, the fisheries industry is concerned with perhaps a few percent, so hardly any marine organisms are used.
The fishery industry's main mode of production is the exploitation of wildlife living in the natural environment. Breeding and aquaculture in the sea or inland waters amounts to the same thing. In this respect, the fisheries industry mode of production differs from that of terrestrial agriculture and livestock husbandry, where people raise and manage animals that have been selectively bred for a long time. Further, the fish and shellfish exploited by the fisheries industry are subject to a phenomenon not seen in species used for land-based food production in that some species include tissues that are highly toxic, while other species become toxic due to changes in their habitats, which are natural phenomena.

2. Functions of Fishery Products

Epidemiological studies indicate that human disease incidence rates are lower and lifetimes are longer in regions where people eat much rice and fishery products, and fishery products have an established reputation as healthful. In fact, seafoods are rich in high-quality proteins, lipids, vitamins, minerals, and more, and are excellent as a source of nutrients. It is known that the n-3 OK polyunsaturated fatty acids such as icosapentaenoic acid (IPAOK), which are plentiful in blue-backed fish such as sardines and mackerel, have effects such as lowering levels of blood cholesterol and neutral fats. Moreover, although there is variation in the methods and levels of scientific assessment underpinning the claims, it is reported that seafood constituents have many kinds of bioactivity including antibacterial activity, hypotensive activity, antioxidative activity, immunomoduratory activity, and antitumor activity.
IPA OK is the only functional active substance exhibited by seafood that has been identified and developed into pharmaceuticals, but there have been vigorous efforts in the development of functional foods in the quest for higher added value. As a result, there are many seafood-derived substances used as constituents in "foods for specified health uses", which are authorized by the Minister of Health, Labor and Welfare, and substances used as the ingredients in so-called "health foods", which require no particular permission or authorization.
This year "specific medical checkups and health guidance" started with the aim of improving the situation in which many middle-aged and elderly Japanese are said to be at risk of developing lifestyle diseases. And on a daily basis advertisements feature words such as "metabolic", "health", "health foods", "supplements", and "natural foods". Although people understand the importance of improving energy-excessive dietary habits and eating balanced meals, they cannot easily change their meat-rich diets due to reasons such as price, convenience, and preferences. People think, "Well then, we'll switch to health foods and supplements"; but perhaps these are products of our era that were created by the desire of Modern Man to obtain "health" without any effort.
While health foods and related merchandise are said to have built an 800 billion-yen market, there are now concerns about problems of excessive expectations for their efficacy and about excessive use. Moreover, products whose ingredients and labeling are illegal, whose efficacy is suspect, and which have caused health damage and economic loss are confusing consumers who want health foods to be "worry-free". It is very attractive to seek added value in the "biological regulation function" of food, which is said to be its tertiary function; however, trustworthy claims about functionality need to be supported by medical and dietetic evidence, which is a high barrier to clear.

3. The Safety of Fishery Products

We are fairly well versed in the kinds and ways of eating fishery products: there are no people who eat the liver or ovaries of Tetraodontidae species, we know what fish and shellfish caught on the coast are edible, which taste good and which do not, which are toxic and which parts of them are toxic, and we know to blanch seaweed in boiling water before eating. If fishery products are left sitting they will readily spoil and cause food poisoning, but there has been a sense of faith that fish and shellfish from near-shore waters are safe to eat.
To secure a source of protein in the postwar years, the development of new fisheries such as pelagic fisheries in distant waters and deep-sea trawling was promoted vigorously, which brought totally new species to our dinner tables along with Japanese-sounding names attached to them. Among the fish caught in distant waters and imported from foreign countries, people have found fish containing constituents whose safety cannot be confirmed, and those that closely resemble offshore species of Tetraodontidae whose flesh is highly toxic. With instances of food poisoning from South American fish resembling the Pacific rudderfish (Psenopsis anomala) and the green toadfish caught in Vietnamese waters, which resembles Takifugu spp., the Japanese are finding that their "common sense" gained through experience with fish from Japan's near-shore waters does not work with fish from other countries.
Recently a person who ate rocky porgy at a restaurant suffered ciguatera and filed suit against the chef under the Product Liability Law. The court said that other cases of ciguatera from the fish had occurred in Okinawa, rejected the claim that the defendant could not have had foreknowledge of its toxicity, ruled that the defendant could not avoid "the liability of the manufacturer in processing and providing poisonous fish", and recognized the plaintiff's claim for payment of damages. This court decision will likely become a precedent that restaurants that prepare and provide poisonous fish and shellfish have "product liability". Henceforth, people involved in the distribution and consumption of fishery products will need specialized knowledge on not only the characteristics of fishery products, but also on the safety of poisonous fish and the like.
Especially problematic with poisoning from natural toxins in fishery products are ciguatera and shellfish poisoning. Both types of food poisoning are caused by a natural phenomenon, the toxification of fish and shellfish by the blooms of toxic dinoflagellates. Because one can safely eat the same fish and shellfish from marine areas where toxic dinoflagellates are not present, there is great danger to importers and recreational fishers who lack knowledge and experience. We need to be aware that the presence of poisonous fish and shellfish previously limited to certain marine and geographical regions is now a direct danger that threatens the health of people around the world owing to globalized distribution of aquatic products. Shellfish that are especially popular worldwide sometimes cause fatal food poisoning, as with paralytic shellfish poisoning, and it is essential to monitor the toxicity of not only domestically produced fishery products, but also those imported.
To people who lived near the sea, fish and shellfish were a valuable, comparatively easy-to-obtain food. As one can see from the Tetraodontidae bones found among the fish bones in the shell mounds throughout Japan, people were also familiar with poisonous species. To safely enjoy the taste of fish and shellfish and to create our current healthful "fish-eating culture", there was no doubt much trial and error involving sacrifice. It is our responsibility to take the new knowledge about safety and functionality obtained with the latest science, incorporate it into this culture, and correctly communicate it to the next generation.

4. Securing Fishery Products, and Marine Life Sciences

Marine ecosystems are built on a subtle balance among species that depend on that special environment called the ocean. It is the phytoplankton, microorganisms, and other autotrophic microorganisms and the primary producers that provide organic matter to marine organisms and sustain marine ecosystems. The food chain is composed of the zooplankton and other primary consumers (which are also secondary producers), as well as carnivorous and other high trophic level predators (which are also producers). The fisheries industry takes fish and shellfish that are at the top of the food chain. Therefore, it is possible that this balance will be disrupted not only by overfishing of species sought by the fisheries industry, but also by pollution of the marine environment that disturbs the amounts and distributions of plankton and of fish and shellfish lower on the food chain. It is also undeniable that overprotection of certain species affects the food chain. From a quite early time the fisheries industry was asked to make itself into a resource-protecting, environment-conserving industry that strives to peg catches to stocks. Ensuring that fishery products are sustainable means catching the surplus portion while leaving enough of a resource to reproduce itself. It is hard to imagine developing a fisheries industry that is compatible with resource protection while not having an understanding of marine ecosystems, such as the life stages of the target fish and shellfish from　hatching to sexual maturity or its own relationship with many species and the marine environment.
Analyses of marine ecosystems have been carried out in fields such as population ecology, community ecology, and the environmental sciences. Recently the most advanced chemical and biochemical technologies have been enthusiastically introduced in marine ecosystem analyses??? and research in this field has achieved a quantum leap. In the present lecture, I would like to focus on t he physiologically active substances that provide valuable information for elucidating on a molecular level the interactions between organisms of the same and different species. There are many instances in which research on the treatment and prevention of food poisoning by marine organism toxins, or on detection methods, has led to the development of new pharmaceuticals and biochemistry research reagents. There are unlimited possibilities in both basic and applied marine life science research that will be useful in securing fishery products and in their safe consumption. At Kitasato University as well, it is important to conduct free, lively discussions with researchers in various fields about subjects including the current state of research on marine organisms, challenges for and impediments to carrying out research, and new research ideas, as well as to arrange and facilitate distinctive research with the purpose of shedding light on marine ecosystems.

Introduction

Recent trends in Japan toward a more "Westernized" dietary lifestyle have been accompanied by health problems due to excessive fat consumption. In the 10-year period between 1960 and 1970, human consumption of animal fats quadrupled in Japan, an increase of unprecedented suddenness anywhere in the world. Because excessive fat intake leads to conditions such as myocardial infarction and obesity, the MHLW has cautioned against excessive consumption of animal and vegetable fats in "The Dietary Reference Intakes for Japanese". In addition to cautioning against excessive fat consumption, the MHLW also recommends well-balanced fatty acid intake. Fatty acids can be classified as saturated, monounsaturated, and n-3 and n-6 polyunsaturated fatty acids, and the saturated fats, which make up a high proportion of most animal fats, have been associated with elevated blood cholesterol levels. In this regard, studies have shown that the incidence of myocardial infarction is much lower among Eskimos whose dietary fat comes primarily from fish oil having a high content of n-3 polyunsaturated fatty acids, than among Danes whose diet is focused on meat and other products containing a high proportion of n-6 polyunsaturated fatty acids and saturated fatty acids. These findings suggest that the n-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play an effective role in preventing myocardial infarction, which has led to a call for greater fish consumption in Japan.
The n-3 fatty acids contained in fish oil are also known to inhibit cancer cell proliferation. The mechanism by which this occurs remains unknown, but recent experiments in nude mice raised on fish oil have shown that n-3 fatty acids promoted apoptosis and inhibited cancer cell proliferation. Detailed research into the mechanism of apoptosis is currently underway across a variety of fields, and numerous inducing and inhibiting factors have been discovered. However, the mechanism of apoptosis induction remains poorly understood, particularly regarding the mechanism of release of pro-apoptotic factors from the mitochondria. The mitochondria are the largest cell organelles producing reactive oxygen species (ROS), and some reports indicate a relationship between ROS and apoptosis induction. Such findings suggest that clarification of the relationship between EPA, active oxygen, apoptosis induction, mitochondria, and inhibition of cancer cell proliferation could be a research project of considerable interest.

Mechanism for EPA-induced Apoptosis

We investigated the mechanism of EPA-induced apoptosis, Rat basophilic leukemia cells (RBL-2H3 cells) treated with EPA showed induction of apoptosis that was both concentration-dependent and time-dependent. Apoptosis was similarly induced by the n-3 fatty acid DHA, but not by the n-6 fatty acid linoleic acid or by saturated or monounsaturated fatty acids. Factors such as cytochrome c and apoptosis-inducing factor (AIF), which determine the activation of apoptosis, are released by the mitochondria. Through investigations using agents to inhibit those activating factors, it has become clear that AIF contributes to EPA-induced apoptosis. EPA produced notable increases in intracellular calcium concentration, while apoptosis induction was inhibited by ruthenium red, which blocks mitochondrial calcium influx, suggesting that the flow of calcium into the mitochondria is essential for apoptosis induction. This mitochondrial calcium influx was associated with a pronounced increase in the formation of the active oxygen species hydroperoxide, and apoptosis was blocked by the addition of Mn-TBAP, which eliminates the mitochondrial superoxide. Furthermore, overexpression of the phospholipid hydroperoxide glutathione peroxidase (PHGPx, a unique antioxidant enzyme that eliminates intracellular phospholipid hydroperoxide) in the mitochondria of RBL-2H3 cells was associated with elevated mitochondrial calcium levels, but with no induction of apoptosis. These findings suggest that the formation of hydroperoxide due to elevated mitochondrial calcium, and also the PHGPx substrate phospholipid (phospholipid hydroperoxide) contribute to the AIF released from the mitochondria. In cells overexpressing mitochondrial PHGPx, there is strong inhibition of apoptosis induced by factors such as ultraviolet irradiation, staurosporine, and deoxyglucose, as well as by EPA.
We attempted to identify phospholipid hydroperoxides related to the mitochondrial release of apoptosis inducing factors such as AIF and cytochrome c. In considering mitochondrial release of apoptosis inducing factors, we felt that we should focus on cardiolipin, a phospholipid found specifically within the mitochondria. A permeability transition pore (PT pore), which is a megachannel in the mitochondrial membrane, must be opened in order for the apoptosis inducing factor to be released from the mitochondria. The mitochondrial protein that controls the opening and closing of this channel is the adenine nucleotide translocator (ANT), also known as the ATP/ADP translocator. Cardiolipin, which is essential for ANT activity, contains a high concentration of polyunsaturated fatty acids in comparison to other phospholipids, and is readily oxidized as compared to other phospholipids . Because cardiolipin hydroperoxide was detected in the mitochondria of EPA-treated cells, we decided to use ANT-reconstituted liposomes to review the effects of cardiolipin hydroperoxide on ANT activity. ANT activity was noted in the presence of liposomes including cardiolipin, but was strongly suppressed by the addition of cardiolipin hydroperoxide to the reconstituted liposomes. Our findings indicated that mitochondrial production of cardiolipin hydroperoxide resulted in deactivation of ANT and opening of the PT pores. In addition, cytochrome c has an affinity for cardiolipin in the inner mitochondrial membrane, and bonds loosely to that inner membrane, so in order for cytochrome c to be released, it must be free from the inner membrane to the intermembrane space. When we investigated the affinity between cytochrome c and cardiolipin, we found that affinity to be stronger than between cytochrome c and other phospholipids. However, affinity to the oxide form (cardiolipin hydroperoxide) was extremely weak. Cardiolipin hydroperoxide also greatly affected the stability of the mitochondrial membrane. When the mitochondria were isolated from the cells, the mitochondrial membrane that had integrated with the cardiolipin hydroperoxide became extremely unstable, and mitochondrial swelling and the release of apoptosis induction factors were readily elicited. These findings indicate that the EPA-induced elevation of mitochondrial ROS levels resulted in oxidation of the unsaturated-fatty-acid-rich cardiolipins, deactivation of ANT, destabilization of the mitochondrial membrane, and release of apoptosis activating factors from the mitochondria, thus inducing apoptosis.

Lipid Peroxidation and Male Infertility

The intracellular enzyme PHGPx, which is responsible for reductionof phospholipid hydroperoxides, is strongly expressed by sperm cells. Our investigation showed this expression to be localized in the midpiece of sperm where almost all mitochondria are present. Just as in lymphocyte formation, the sperm formation process requires active apoptosis in order to maintain cell quality.
As I order to investigate the involvement of mitochondrial PHGPx, an apotosis-inhibiting factor, in sperm formation, we studied PHGPx expression in the sperm of infertile men who were defected the production and mobility of sperm. We found marked reduction in the expression of PHGPx in the sperm of 7 out of 73 infertile male patients. Those patients showed mitochondrial swelling in the sperm, and morphological abnormalities were apparent. Assessment of patients on the basis of WHO classifications for male infertility indicated that, in the category of male infertility patients with low expression of PHGPx, all 7 patients were classified as having serious male infertility with oligozoospermia (low sperm count) and with most of the live sperm showing asthenozoospermia (reduced sperm motility). Approximately 30% of these male infertility patients showed low levels of PHGPx expression, indicating that decreases in the expression of PHGPx seriously interfered with sperm function.
In order to gain a direct understanding of the contribution of PHGPx to sperm formation and function, we created a PHGPx knockout mouse, but the phenotype was embryonic lethal. We then used the Cre/loxP system to create a testicular PHGPx-specific knockout mouse. Mice created specifically to be deficient in testicular PHGPx showed abnormal mitochondrial morphology in sperm and pronounced reductions in sperm count and fertility, indicative of potent effects on differentiation and function in sperm with reduced expression of PHGPx. We believe that the reduced expression of PHGPx in the sperm mitochondria led to elevated mitochondrial levels of phospholipid hydroperoxide, that oxidative stress can develop in sperm due to a variety of factors, and that this oxidative stress can result in the formation of phospholipid hydroperoxides which may be closely related to male infertility.

Introduction

Since BSE (bovine spongiform encephalopathy) first appeared in Japan, there has been increasing concern about food safety, and recently a number of problems have emerged regarding "truth in labeling" for a variety of food products ranging from beef, pork, and chicken to chocolate and manju (steamed filled buns). However, these problems have not caused actual injury to humans, for example through hospital admissions due to illness (the "imported gyoza affair", in which contaminated frozen gyoza from China were sold without being labeled as imports, may turn out to involve criminal action, but that is a separate issue from foodborne diseases).

In sharp contrast, when we consider human dietary health issues it is clear that foodborne diseases can result in actual human fatalities. There is nothing more serious than the death of a human being, and this is the point of view from which I approach food safety.

At present, under the Food Safety Basic Law established in May 2003, the Food Safety Commission has been set up independently from governmental institutions (risk-management institutions) such as the Ministry of agriculture, Forestry and Fishery (MAFF) and the Ministry of Health, Labor and welfare (MHLW), which are responsible for risk management through means such as regulation and guidance. The Food Safety Commission was made independent from these other institutions in order to promote science-based food safety administration, and to provide an objective, neutral, and fair-minded scientific assessment of the effects of food on health.

In this article, I will describe the risk assessment targets currently being pursued by the Food Safety Commission joint committee for the review of microorganisms and viruses: (1) Salmonella contamination of chicken eggs and (2) Campylobacter contamination of poultry meat. I will describe the conditions under which such contamination occurs on farms, and will discuss countermeasures.

1. Salmonella Contamination of Chicken Eggs

Japan currently imports nearly 1,000,000 chicks for breeding use per year. Laying hens that are the offsprings of these chicks maintained during their egg production cycle, and the eggs laid are used for food. If the imported breeding chicks are contaminated with Salmonella enteritidis (SE), this SE will pass transovarially to the next generation of the imported chicks (laying hens) and subsequently contaminate the eggs laid by those hens. Since 1989, the incidence of SE food poisoning increased sharply in Japan, becoming a nationwide problem. In the 1990s, Salmonella was in competition with Vibrio parahaemolyticus for the most common cause of foodborne iseases in Japan. However, the MAFF and MHW implemented policies including stronger import quarantine measures and "best if used by" labeling for commercially marketed eggs, and a variety of countermeasures were also implemented by Japanese poultry farmers. These measures brought a reduction in Salmonella cases beginning in 2000, and during the last few years the incidence of Salmonella foodborne disease has dropped sharply in comparison with the incidence of Campylobacter and norovirus, the two other most common causes of foodborne diseases.

1) Status of Outbreaks on Poultry Farms

In the 1990s, approximately 15% of poultry farms tested was positive for SE contamination. By 2001, this number had dropped to 3.5%, and today the number is believed to stand at 1%-2%.

2) Countermeasures at Poultry Farms

• Vaccines: SE inactivated oil-emulsion vaccine is considered to be effective in inhibiting the production of contaminated eggs. At present there are five companies providing a total of six products in this field, and our research laboratory has participated in the development of each of those products. Since the incidence of contaminated egg production is approximately 1 in every 3000 eggs, it is difficult to prove the efficacy of these vaccines, which currently are officially indicated for "reducing bacterial colonization within the intestinal tract".
• CE (competitive exclusion) method:　Immediately after chicks hatch, they have a gastrointestinal tract that is bacteria-free. Such chicks will die following the oral administration of just a few Salmonella bacteria. If during this period of high sensitivity the chicks are treated with anaerobic cultures derived from the cecum content of healthy adult chickens, they will develop normal bacterial flora, and Salmonella that subsequently invades into the gastrointestinal tract will be competitively excluded. This technique is a form of probiotics, and is used worldwide.
• Feed additives:A number of feed additives are available. However, our research shows that not all of them are effective. One that has proven effective in reducing SE colonization within the intestinal tract is the natural drug Curcuma zedoaria.

3) Primary Measures Employed Overseas (Private-sector-led)

• England:Breeders and laying hens that are found to be infected by SE are destroyed. Eggs are stored at 20°C, and the "best if used by" date is set at 27 days after laying or 21 days after packing.
• USA:Eggs are stored refrigerated at 7.2°C, and are shipped under refrigeration.

2. Campylobacter Contamination of Poultry Meat

1) Transovarial Infectivity of Campylobacter jejuni
1986-1997: Vertical infection ruled out

• Attempts to experimentally induce eggshell penetration were unsuccessful.
• Inoculation into the egg albumin resulted in only a few positive chicks after hatching (12/162)
• Breeding hens and their chicks differed in serotype for the Campylobacter strains that were isolated.
• Breeding hens and their chicks differed in RFLP type for the Campylobacter strains that were isolated.

After 2000: Vertical infection confirmed

• Same clonal strains isolated from breeding hens and their chicks
• Isolation of Campylobacter from oviducts of breeding hens and laying hens
• Isolation of Campylobacter from residue in incubators
• Detection of Campylobacter DNA in the intestinal tract of chick embryos during incubation

2) Contamination Status of Broilers, and Shipping to Poultry Processing Plants

Campylobacter infection generally occurred in the chicken flocks when the chickens are approximately 3?5 weeks of age, after which point drinking water becomes contaminated and infection spreads rapidly throughout the flock. At present, 70%?80% of chicken farms in Japan are believed to be contaminated. During shipping to the poultry processing plant, the shipping cargos also become contaminated, which can considerably accelerate the general level of contamination.

3) Routes by which Campylobacter Invades into Farms

No clear theories have yet been formulated regarding exactly how Campylobacter is introduced into poultry flocks. Rather than conducting in-depth research on bacterial infiltration routes into the facility, many researchers have reported on transmission routes for infection within the poultry flocks. In most cases, bacteriologic test findings are negative for the source of water supply and for feed. Vectors of bacterial transmission within the facility may include employees as well as flies and other insects. Further possibilities include vertical infection, manura, small mammals, and environmental factors. Since the air can be eliminated as a sustained source of infection (transmission source), the primary source of infection (transmission source) at farms is most likely to be fecal contamination of the drinking water.

4) Countermeasures

• Mucosal competitive exclusion:Experiments with mucosal competitive exclusion proved to be effective when using anaerobic culture from mucosal curettage of the cecum from 6-week-old broilers.
• Probiotics:Probiotics including poultry-specific Lactobacillus acidophilus and Streptococcus faecium inhibit intestinal colonization by Campylobacter (27% decrease), and also inhibit Campylobacter shedding (70% decrease). Some reports indicate that the effectiveness of probiotics differs between Salmonella and Campylobacter. Saccharomyces boulardii (a strain of yeast) has been shown to be effective against Salmonella, but not against Campylobacter. This is probably because Campylobacter shows no mannose-specific binding such as seen with Salmonella.
• Prebiotics:There are reports of the effectiveness of adding 4% sucrose and 0.7% caprylic acid (neutral fatty acid) to the feed.
• Bacteriocins:Bacteriocin OR-7 isolated from Lactobacillus salivarius is reported to demonstrate antibacterial activity against Campylobacter in vitro and in vivo. At first look, this substance appears extremely effective. However, in the case of the in vivo study used day-old chicks, I suspect that the conditions within the gut of such young chicks are not yet well-suited for explosive Campylobacter proliferation. Even if chicks of that age are inoculated with 108 CFU, the bacteria will be unable to colonize the as-yet-undeveloped intestinal crypts, and will simply proliferate within the intestinal lumen. If bacteriocin is administered at this stage, the bacteria will be extinguished, but it is questionable whether this is true antibacterial activity. It is important that antibacterial effects can be observed even close to the shipping time, so we would like to see results for testing performed from 5 weeks old until immediately before shipping.
• Bacteriophages:The Campylobacter colonization-decreasing effect of bacteriophages was investigated using 25-day-old chicks in which Campylobacter colonization had already occurred. Chicks were orally inoculated with phage and were then monitored for 5 days. Reductions ranging from 0.5 log to 5 log were noted, with the effectiveness varying depending on the combination of Campylobacter strain and the phage types.
• Vaccines:To date, results have been presented for a number of vaccine types including live vaccine, inactive vaccine, recombinant vaccine, and DNA vaccine. These vaccines have been reported to range from completely ineffective through slightly effective to extremely effective, with the latter represented by preparations such as the recombinant vaccine that was created by incorporating Campylobacter-related genetic material into attenuated Salmonella.
  Chicks that had not yet been given either food or water were inoculated orally with this attenuated Salmonella recombinant vaccine (108 CFU) 4 hours after hatching. Follow-up immunization was administered 2 weeks later, and after an additional 2 weeks, the chicks were orally challenged with a wild-type Campylobacter. Chicks were subsequently monitored for increases/decreases in Campylobacter. Results showed that the live bacteria count decreased by 6 log or more in the vaccinated group in comparison to the control group. This is due to induction of serum (IgG) and intestinal (IgA) antibody production against Campylobacter.

5) Poultry Processing Plants: Cross-contamination and Logistic Slaughter

When broilers are contaminated with Campylobacter at a farm and that contamination is further exacerbated during shipping, the slaughtering process at the poultry processing plant further adds cross-contamination, which can result in even Campylobacter-free broilers becoming contaminated. Generally, the number of bacteria on the poultry carcass is reduced by washing with hot water, increased by the defeathering and evisceration, and then reduced again by chilling. However, cross-contamination can occur in particular in chilling water, with increased contamination both of chicken carcasses and of chicken meat.
In order to avoid such cross-contamination, the Codex Alimentarius Commission created jointly by WHO and FAO to develop food standards has provided a special recommendation that infected poultry should be slaughtered on weekends, or at least at the end of the working day. Countries such as Sweden, Denmark, and Ireland, where the poultry processing plants are relatively small in scale, have adopted and are implementing these recommendations, and are finding them to be quite effective. However, it remains questionable whether such a system is feasible in Japan. Problems include the following. (1) Some producers have schedules in place at least 6 months in advance for chick delivery dates, growing periods, hire dates for chicken catchers, shipping dates, and disinfection of empty chicken sheds. It would not be a major problem if the chickens are slaughtered in the afternoon of the scheduled day, but it is unfeasible in such cases to postpone the slaughter date for several days until the weekend. (2) Large poultry companies may have poultry processing plants at two or three separate locations, so in theory it would be possible to classify incoming chickens as "clean" or "carrier", and to process those groups separately. However, this could lead to considerable confusion if the plants are located at some distance from each other. Furthermore, in order for the processing plant to obtain clear test results and to take appropriate measures, test specimens must be collected 2 weeks before shipping. This means that the processing date is determined 4 to 5 days before shipping (less if PCR is used). (3) In a situation such as we have currently, where the majority of poultry is contaminated, this method will not be very effective. It should, however, prove more useful when we are able to reduce the amount of contaminated poultry (to a contamination rate of 20%?30%).

Conclusion

When Salmonella contamination of poultry eggs developed into a national problem, producers became the recipients of societal sanctions. Those sanctions, together with new regulations from the MAFF and the MHLW and greater awareness by producers, have led to continued reductions in the incidence of SE foodborne diseases.
In contrast, Campylobacter contamination of poultry meat is completely unregulated. The issue has received almost no attention from the mass media, and producer awareness is low. Currently, risk assessment is being conducted by the Food Safety Commission. As a member of that Commission, I am monitoring the Commission's progress and stating my opinions.
The primary issues regarding Campylobacter foodborne diseases are (1) contamination at the poultry farm, (2) cross-contamination at the poultry processing plant, and (3) inadequate cooking of poultry and the consumption of raw meat such as chicken gizzard, liver and so on. In this article, I have not addressed the issues at the consumer level. However, although the foundation of foodborne disease countermeasures lies in the progression of Farm → Poultry Processing Plant → Meat Processing and Transport → Consumption, Campylobacter does not proliferate at the meat processing and transport stage because of the microaerobic environment there, so assessment is easily implemented. However, at poultry farms it is difficult to specify the source of infection and of transmission, which makes it much more difficult to prevent bacterial invasion. There is also the additional difficulty, not commonly seen overseas, of the Japanese cultural proclivity for eating raw gizzard and liver and other forms of raw meat. More time will be required to resolve these problems, and that resolution will require the cooperation of everyone involved with the process, from the farm to the poultry processing plant, the meat processing and transport industry and the consumer.

Arsenic and Health Damage in Recent Years

1. Arsenic, representative of which is arsenic trioxide, is a typical poison that has been used for homicide and suicide from Middle Ages Europe until modern times. Arsenic trioxide is a byproduct of copper refining, and is also made from arsenic sulfide. From 50,000 to 60,000 t are used annually in Japan, with primary applications being LCD glass substrates and semiconductors with arsenic compounds. There are concerns about health effects from occupational exposure. Because in the past much arsenic was used in applications such as pesticides, herbicides/defoliants, and wood preservatives (chromium-copper-arsenate, or CCA), there is much soil seriously contaminated with arsenic, and much discarded CCA-treated wood. There were very many cases of skin and lung cancer owing to occupational arsenic exposure and owing to the inorganic and organic arsenic compounds used in pharmaceuticals (such as tonics and compounds used to treat syphilis, infections, and parasites). Currently the spotlight is trained on the apoptosis effect arsenic trioxide has on cancer cells, and it is now used in drugs for treating acute leukemia (acute promyelocytic leukemia, APL).　

2. About 70 years ago, Japan manufactured 7,000 t of chemical weapons, many of which contained arsenic. Even now, 4,000 t (300,000?400,000 artillery shells) remain in China, and 3,000 t in Japan. Currently in Japan, about 160 people poisoned by arsenic chemical weapons are receiving treatment, and in China, there are accidental deaths and injuries related to chemical weapons.　

3. In recent years, mainly in Asian countries, pumped wells (15?20 m) have been dug for the purpose of preventing water-borne communicable diseases and securing water for agriculture. However, well water is contaminated with naturally high concentrations of inorganic arsenic compounds. According to statistics of international agencies, there are about 80 million victims of chronic arsenic poisoning, including potential victims, and there is a worsening trend in East Asia.

4. In July 2004, the UK Food Standards Agency (FSA) recommended a ban on the consumption of hijiki seaweed in the UK out of concern for the health effects of the high concentrations of inorganic arsenic in hijiki, and UK actions in this regard were widely reflected in other Western countries. As a result, hijiki is now eaten only in Japan. In March 2004, the author and others prepared a report for the Food Safety Commission entitled "Report on a Review of Basic Documents on the Assessment of Arsenic in Hijiki". In the interests of caution, basic research has also been started on the health impacts of arsenic compounds in other seaweeds (such as kombu, wakame, and nori）.
Arsenic has a mechanism of action absent from other metals and metaloid elements. Arsenic's chemical structure and chemical morphology strongly influence the biological effects of arsenic compounds on humans and these effects are not determined solely by "amount of exposure" or "amount ingested". Because arsenic compounds are intimately connected to our food and living environments, it is essential to manage the risk of acute and chronic poisoning and carcinogenicity. A problem related to this, and which is now the focus of attention, is the health effects of arsenic compounds from excessive consumption of seaweeds.

Chemical Forms and Concentrations of Arsenic in Seaweeds

An environmental characteristic of arsenic compounds is that many are found in higher concentrations in marine organisms than in terrestrial flora and fauna. While the concentrations of arsenic are low in plants cultivated and produced in the soil and in livestock products, the concentrations of total arsenic detected in some seaweeds, fish, and shellfish range from several to several hundred ppm (μg/g), and the difference between food groups from terrestrial and marine organisms is perhaps 1,000 times. Even among marine organisms, there are large differences between the chemical structures of arsenic compounds found in seaweeds and those found in fish/shellfish. The latter contain the trimethyl arsenic compound arsenobetaine (AsB), which has no acute toxicity, and an LD50 value of 10 g/kg, which is 1/300 that of arsenic trioxide (LD50: 0.03 g/kg). AsB has low tissue affinity, it is quickly eliminated along with urine, and its half-life is 3?5 h. By contrast, the concentrations and chemical structures of arsenic in seaweeds are complex. The arsenic detected in seaweeds can be roughly divided into the two categories of inorganic arsenic and dimethyl arsenic compounds. Inorganic pentavalent arsenic is detected in the brown alga hijiki, and the concentration of inorganic pentavalent arsenic in commercially sold dried hijiki is high at 10?100 μg/g. The arsenic detected in other seaweeds (such as kombu, wakame, and nori) comprises mainly arsenosugars (As-Sug), which include many forms . At least 20 kinds have been confirmed, and they are present in high concentrations of several ppm to several tens of ppm. Limited research performed on mammals shows that As-Sug are metabolized and decomposed by the liver and intestinal bacteria, changed into dimethylarsinic acid (DMA), and eliminated in the urine. This DMA is the same as the metabolite of arsenic trioxide. Although the LD50 values of As-Sug have not been precisely calculated, because that of the metabolite DMA ranges between 1,300 and 1,500 mg/kg, there are likely no concerns about acute toxicity. However, because arsenosugars are transformed into DMA in the body, the problem is not that of impacts from acute and chronic toxicity, but of carcinogenicity risk.　

Field Study

"Arsenic Ingestion and Health Effects in People Who Consume Much Seaweed"
 
Research study and method: Our study area was the Iwate Prefecture coastal zone, and subjects totaled 119 people (59 men 51.4±14.0 years and 60 women 52.1±12.9 years), comprising 79 people who grow wakame and engage in abalone and sea urchin aquaculture, and their families, and 40 people who engage in sea squirt aquaculture, and their families. We conducted a meal study with the "duplicate portion system", recovered samples of all the food and beverages for subjects separately for breakfast, lunch, dinner, and snacks, and took spot urine samples on the same days. At the same time, we gave questionnaires to subjects on their dietary lifestyle and health condition, and conducted health examinations. We treated meal samples with the nitric acid ashing method and obtained the total arsenic concentration with inductively coupled plasma atomic emission spectrometry (ICP-MS). We measured arsenic compounds in the blood according to chemical species (inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA), and AsB by pretreating samples with alkaline thermolysis and then using the cold trap?reduction?atomic absorption method. To determine oxidative DNA damage, we measured the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the urine with the ELISA method. Arsenic and 8-OHdG in urine were corrected with the concentration of creatinine in urine. As our control group, we used the concentrations of arsenic and 8-OHdG in the urine of 248 adult men and women living in six areas of Japan, and who were found healthy by medical examinations.　

Daily Amounts of Seaweed, Fish, and Shellfish from Meals

In this study, none of the subjects ate hijiki, while most ate wakame. While in general a Japanese eats about 14 g of seaweed daily, the average for the 119 subjects in the experimental group tended to be higher at 21.8±26.6 g Further, there was a pronounced difference between men and women, with women eating the large amount of 28.2±28.2 g, and men 15.2±23.3 g. The experimental group's amount of fish and shellfish was 108±71.7 g, which was not different from the national average (about 106 g). However, we noted that in the experimental group the men (121±75.5 g) tended to eat more than women (96.6±66.2 g).

Daily Amount of Total Arsenic Ingested from Food
 
In Japan's culinary culture the Japanese eat more seaweed, fish, and shellfish than other ethnic groups, and from this it has been known that they tend to inevitably ingest more total arsenic from food. In 1992, the author used the same "duplicate portion system" to conduct a survey of city dwellers (35 men and women in Kawasaki City) and found that their total arsenic consumption was 195±235 μg/day. The result obtained by Mohri et al. in Fukuoka City was similar at 202±143 μg/day. In this study, the average daily total arsenic consumption of the 119 subjects was 336±417 μg/day, which was nearly twice the amount for city dwellers. The average value for women, 374±546 μg/day, tended to be larger than that for men, 297±216 μg/day, but no statistically significant difference was found between them.　

Urine Arsenic Concentrations and Chemical Forms
 
The average urine arsenic concentration by chemical species of the 248 healthy Japanese was 149±129 μg/g creatinine (iAs, 2.4%; MMA, 1.3%; DMA, 26.8%; and AsB, 69.1%). This study found that the average urine arsenic concentration of the 119 subjects was high at 304±391 μg/g creatinine (iAs, 0.5%; MMA, 2.5%; DMA, 36.8%; and AsB, 60.2%), which was about twice the average value for the 248 people in the control group. The average value for men was 251±202 μg/g creatinine (iAs, 0.6%; MMA, 3.4%; DMA, 36.7%; and AsB, 59.0%), and that for women was 357±510 μg/g creatinine (iAs, 0.5%; MMA, 1.9%; DMA, 36.7%; and AsB, 61.0%), revealing that the average value for women is higher than that for men.
During the study period women ate much wakame, whose primary type of arsenic is As-Sug, and the fact that As-Sug's metabolite is DMA could explain the rise in urine DMA concentration. Hence, the results showed a significant correlation (r=0.357) between the amount of seaweed eaten and urine DMA concentration. There was also a significant correlation (r=0.375) between the amount of fish and shellfish eaten and urine AsB concentration.　

Arsenic Ingestion and Oxidative DNA Damage
 
Currently 8-OHdG is widely recognized as an effective marker of oxidative DNA damage. The average urine concentration of 8-OHdG in the 248 healthy people was 15.4±5.60 ng/mg creatinine. The value for the 128 men was 15.2±5.19 ng/mg creatinine, while that for the 120 women was 15.6±5.49 ng/mg creatinine, revealing no discernible differences for gender or age (ages 20-65).
The average urine 8-OHdG concentration of the 119 study subjects was 17.3±6.79 ng/mg creatinine, which tended to be somewhat higher than that of the control group, but we found no statistically significant difference between the groups (p<0.01). Values for men and women were, respectively, 17.6±6.98 ng/mg creatinine and 17.0±6.64 ng/mg creatinine (no significant difference). We found no statistically significant difference between the urine 8-OHdG concentration of the 119 study subjects and the amounts of seaweed, fish, and shellfish consumed, and there was no correlation between the urine arsenic concentration by chemical morphology and urine 8-OHdG concentration.

Conclusion

It is widely acknowledged in society that seaweed is a beneficial food from a dietetics perspective, but as this research showed, the daily total arsenic amount ingested by fishery workers and their families, who eat much seaweed, fish, and shellfish, tends to be higher than that of city dwellers. There is particular concern with regard to the significant correlation between the amount of seaweed eaten and urine DMA concentration. This DMA is the same as the main metabolite of inorganic arsenic, and its general toxicity and carcinogenicity make it an important subject for future research. On the other hand, excessive ingestion of AsB from eating fish and shellfish is not considered to present any problems in the way of biological effects because this arsenic is nontoxic.
I feel a need to take good care of Japan's culinary culture, in which hijiki and other seaweeds are eaten, but in consideration of arsenic's toxicity, I think it is necessary mainly in the case of pregnant women, infants, and small children to look elsewhere for a source of minerals instead of using seaweeds as we have been. At the same time, even for adults in general to eat large amounts of seaweed at one time means retaining excessive toxic arsenic in the body, which could increase the risk of cancer. People should be careful not to eat too much at one time.

It goes without saying that basic medical research has in large measure been supported by animal research, but progress in reproductive engineering techniques and the augmentation of basic data on genomes have exponentially boosted the importance of the role that will be played by animal experiments in medical research henceforth. Owing to this trend, laboratory animal facilities not only find themselves required to play a bigger role, but are also pressed to make qualitative changes. From the late 20th century and into the start of this century, the entire genome base sequences of animal species including humans and mice have been determined. This is like having completed a dictionary, and our era (the post-genome era) is now one in which scientists can proceed with biological research with a dictionary in hand. No matter how well one understands the meanings of individual words with the dictionary, that is merely the basis for understanding a foreign language. Similarly, life is an extremely complex phenomenon that can never be understood by just combining simple theories of materialism. In biomedical research, gene functions must be understood in the context of high-order biological control programs such as development, differentiation, and homeostasis in multicellular organisms. Laboratory animals in which certain genes have been transferred, destroyed, modified, or otherwise changed are of great use in analyzing the physiological functions, roles, and control of expression of individual genes (or gene products), as well as the morbid physiology caused by their malfunctioning. Laboratory animals are indispensable to medical research, and they will likely continue holding a permanent place in future biomedical research. In view of this situation, the role and function expected of laboratory animal facilities is now far more extensive than before.
Nearly all the genetically modified animals that are created one after the other are supplied by sources other than designated businesses, but from now on a required condition for laboratory animal facilities will be to provide an environment facilitating their smooth introduction and use. However, at many of the animal facilities now being created, in order to maintain cleanliness there are extreme limits on the exchange of animals with other facilities, but this is harmful because it imposes severe limitations on research. University laboratory animal facilities are not pretty museums for animals, but rather facilities that support research. Improving cleanliness is seen as being incompatible with facility convenience, but need this be really so?

Efforts Made at the Kitasato University School of Medicine's Center for Genetic Studies of Integrated Biological Functions

The Center for Genetic Studies of Integrated Biological Functions, which is a facility of the Kitasato University School of Medicine, is a laboratory animal facility whose design and operation are much different from the usual thinking in order to address this change in demand. Its main characteristics are as follows.

1. It not only maintains a high level of animal cleanliness, but also has a "distribution area" to facilitate smooth distribution. This area can directly accept animals that are somewhat problematic with regard to cleanliness and use them in experiments. When it is necessary to maintain at least three generations, the area has the animals submitted, cleans them, puts them in the SPF(specific pathogen-free) area, and at the same time preserves frozen embryos.
2. Reproductive engineering techniques are integrated into everyday operations, and animal cleaning, embryo freezing, and other activities have become a part of general services. This has facilitated the use of various genetically modified animals that are created in other facilities.
3. Using our distribution area with these functions as a bulwark, we made operating rules for the SPF area that allow no exceptions whatsoever. The SPF area never accepts animals other than those from designated businesses, animals born in the SPF area, or animals cleaned in this facility.
4. In full consideration of user needs, we achieved a quantum leap in convenience by designing traffic lines with very careful thought and rejecting any rules that might be considered unnecessary superstitions.
5. Users are registered under each year's research plan, and have card keys that open only those areas for which they are registered.

The facility has been operating in this manner for six years, and everything is proceeding very smoothly and according to expectations. In the initial period when operating rules were not thoroughly implemented there were several instances in which pathogenic microorganisms made their way into the SPF area, but because all instances were caused by bringing in contaminated animals, thorough implementation of operating rules completely eliminated problems. This is a compact and highly convenient facility, and there are currently few other facilities like it in the world because of the high quality of its animal care environment, including the cleanliness of its SPF area. We believe it can serve as a model for the future design and operation of the animal facilities of universities and other research institutions.

1. Introduction

Underlying the consumer health boom in Japan during recent years is the sale of many probiotic products including fermented milk products. Many of those products have obtained permits to label themselves as "foods for specified health uses". Probiotic products are also increasingly being used as additives for livestock feed. At the same time, the various effects that probiotic products have on biological functions and pathogenic microorganisms are being revealed by science, and even in the domain of medical science, attention is focusing on probiotics as a supplementary treatment.
Behind the spotlight on probiotics is the store of scientific evidence that the makeup of the intestinal microbiota is heavily involved in the host's health, and from the perspective of preventive medicine, work has been done on the development of probiotics that improve intestinal microbiota balance. Further, the latest research is now finding that probiotics not only have just intestinal microbiota-regulating effects, but also that probiotics themselves have functions which directly improve host health. From this perspective, it is perhaps no exaggeration to say that probiotics are a bridge that links "food and medicine", in other words, "agricultural science and medical science". At this symposium I will describe the basic concept of probiotics and the related prebiotics, synbiotics, and biogenics. I will also give an overview of the effectiveness of probiotics and other preparations used in not only foods but also as additives in animal feed, and explore the possibilities of probiotics as a subject for research and education in agromedicine.　

2. The Role of Intestinal microbiota

It is crucial to understand the relationship between the intestinal microbiota and health when exploring probiotics and prebiotics. It is thought that several hundred species of bacteria live in the human intestine, and that 1 g of stool contains at least 1 trillion bacteria, which make up the so-called intestinal microbiota . The intestine's indigenous bacteria maintain a certain flora while living in symbiosis and competing with one another, and they are part of an important biological defense system that functions to keep out exotic pathogenic bacteria. The intestinal microbiota also plays in important role in the development and maintenance of the intestinal immunity system, and it is involved in the onset or suppression of intestinal disorders including infections, allergies, and inflammation. Recently the spotlight has been trained on the role of the short-chain fatty acids that arise in the fermentation process in the colon. Of the short-chain fatty acids it is mainly butyric acid that is consumed in the colon, and it has been shown to have various physiological functions such as facilitating the normal proliferation of colonic epithelial cells, facilitating intestinal movement, governing inflammatory responses, and promoting the absorption of electrolytes. At the same time, butyric acid induces the apoptosis of cancer cells.
Once the intestinal microbiota is established, it is comparatively stable, but if the microbiota is disturbed for some reason, it is possible that an endogenous pathogenicity will be manifested. Further, some species of intestinal bacteria produce carcinogens, bacterial toxins, and putrefied substances such as ammonia and hydrogen sulfide, so if such bacteria continue to be dominant in the intestinal microbiota, it is possible they will have adverse effects such as damaging the intestines or causing colon cancer or other colon disorders. Scientists have shown how the intestinal microbiota is intimately linked to the health of humans (hosts), and attention has focused on probiotics from the perspective of controlling intestinal flora to maintain normalcy.　

3. Probiotics, Prebiotics, Synbiotics, and Biogenics

Probiotics is a concept that contrasts with antibiotics. Its root is an ecological term that signifies probiosis among organisms, and the definition proposed by Fuller is widely accepted: "A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance" 1). Subsequent research has found bacterial strains that have various beneficial effects even if the bacteria are dead, and now these are understood to be "the constituents of microbial supplements or microorganism cells which exhibit effects that are beneficial to the host's health and to maintaining and improving it". The concept of prebiotics is important from the perspective of "improving the intestinal microbiota balance". Prebiotics are defined as "food ingredients that stimulate or activate the growth of certain useful bacteria living in the intestine". Oligosaccharides, yeast extract, and other substances are used. Using prebiotics and probiotics together to improve the intestinal microbiota is synbiotics, another concept that has become widely known. Additionally there is biogenics, proposed as a new concept by Mitsuoka2), who offers this definition: "Food components derived through microbial activity which provide health benefits without involving intestinal microbiota".

4. Lactic Acid Bacteria and Bifidobacteria Gaining Prominence as Probiotics

The bacterial species currently being used or researched as probiotics include those from among these genera: Lactobacillus, Enterococcus, Bifidobacterium, Lactococcus, Clostridium,and Bacillus.Of these, lactic acid bacteria and bifidobacteria are getting the most attention and research because not only are these species found among the intestinal microbiota of healthy people, they have long been consumed in food throughout the long history of humanity, and are therefore thought to be very safe. Many lactic acid bacteria species are also found on the US Food and Drug Administration GRAS (Generally Recognized as Safe) list.

5. Use of Probiotics and Prebiotics by Humans, and Problems

Permission is granted to label a product as a food for specified health uses only when it promises certain healthful effects from the perspective of medical science and dietetics. When a probiotic has been approved as a food for specified health uses, it can be labeled as a "food that regulates one's abdominal condition" (intestinal regulation effect), and this is of great significance. This is because one can expect probiotics to manifest various healthful functions such as by proliferating in the intestines, suppressing the proliferation of putrefying bacteria in the intestines, regulating immune functions, and inactivating cancer-producing enzymes.
Recently, many healthful effects have been reported on the strength of experiments using in vitrocells and laboratory animals and randomized human ingestion tests with placebo controls based on the assessment methods used for drugs. Such healthful effects include infectious disease prevention, allergy prevention, mitigation of inflammatory bowel diseases, and anti-cholesterol effects. Meanwhile, a problem that must be solved is that probiotics have different effects depending on the differences in the intestinal microbiota between individuals. It is difficult to expect that one kind of probiotic will have the same effect in all people. There are now hopes for the development of "tailor-made (order-made) probiotics" that take advantage of the useful intestinal lactic acid bacteria (bifidobacteria) found in all people, and for the development of probiotics adapted to individuals, achieved by advances in research in areas such as analyzing the meta-genomes of an individual's intestinal microbiota. Further, for certain disorders there is promise that probiotics will be effective as supplementary treatment methods in a clinical context. In the United States in particular, there is a trend toward recommending supplementary treatment with probiotics because they are considered effective for treating infectious diarrhea, preventing antibiotic-associated diarrhea, and treating atopic eczema in infants and small children. My personal view is that, in consideration of the characteristics of probiotics, it is difficult to expect efficacy which exceeds that of a supplementary treatment. I think it is preferable to use probiotics from a preventive medicine point of view.
The idea behind prebiotics is to promote the proliferation of useful bacteria among those in an individual's intestinal microbiota. Indigestible oligosaccharides are used as a primary material because they are hard for human digestive tract enzymes to break down, and therefore make their way to the colon and are used by bacteria.
Their function is reported to have the same effect as probiotics. The thinking underlying prebiotics originally arose from the fact that bifidobacteria are more dominant in the intestinal microbiota of breast-fed infants than in infants fed baby formula. Very recently it was discovered that the real bifidobacteria proliferation factor is a disaccharide with the structure of lacto-N-biose, which is found in breast milk. There are expectations for future application in foods, including clinical use for infants who need formula.
Making even more advantageous use of the functions of probiotics and prebiotics is possible through mutual cooperation by experts in the agricultural science field, who are food professionals, and experts in the medical science field, who can prove efficacy in humans from a medical perspective.　

6. The Use of Probiotics for Livestock and Poultry

To promote growth and improve feed efficiency, currently probiotics is approved for use as feed additives. In livestock and poultry production, probiotics are closely watched as substitutes for antibacterial substances (antibiotics and artificial antibacterial preparations), and their use is growing. One underlying factor is concern about the emergence of drug-resistant bacteria due to the use of antibacterial feed additives. Antibacterial substances have been used around the world not only as veterinary drugs for treating disease in livestock and other animals, but also as growth promoters. Especially when used for the latter purpose, there have been concerns that drug-resistant bacteria in animals would be selected for by long-term use, and for such reasons the EU totally banned the use of antibacterial substances in animals for growth promotion starting in January 2006. At the same time, there is dissent in the livestock industry to the idea that contamination by drug-resistant bacteria will widen; for that reason there should perhaps be science-based quantitative risk analyses of the connection between the use of antibacterial feed additives in animals and the emergence of drug-resistant bacteria. In any case, except for a few developed countries, there is a turn toward banning or reducing the use of antibacterial substances for purposes other than disease treatment, making it urgent to develop substitutes for feed additives containing antibacterial substances.
The efficacy of antibacterial substances for promoting livestock growth appear to be mainly mechanisms that work through the intestinal microbiota, such as by (1) preventing potential infections in juvenile animals, (2) improving intestinal metabolism, and (3) suppressing harmful bacteria. However, in probiotics and prebiotics researchers have found effects for growth promotion and feed efficiency improvement that work by the same mechanisms. There are also suggestions that the use of probiotics in livestock and poultry is effective not only from the perspective of reducing the amounts of antibacterial feed supplements used but also from the perspective of preventing illness in animals, eliminating pathogenic microorganisms that create public health problems, and preventing offensive odors by suppressing production of putrefaction products in the intestines. These applications too are receiving attention.
At the Kitasato University School of Veterinary Medicine, we are promoting a materials recycling system of animal husbandry, and we believe that by introducing probiotics into the cycle, we will make an even greater contribution to maintaining and improving animal health, mitigating environmental problems, and promoting food safety. Keeping animal intestines healthy will help bring good-tasting livestock products to consumers, and indirectly help maintain our health.　

7. Train the Spotlight on the Infection-Prevention Effect of Probiotics and Fermented Milk Products!

The author's laboratory is focusing on understanding the role of lactic acid bacteria in the intestines and on the infection-prevention effect of probiotic lactic acid bacteria. We are conducting molecular-level research in several areas from the standpoint of obtaining scientific substantiation.
One research area is anti-adhesion therapy that focuses on the competition that arises between lactic acid bacteria and pathogenic microorganisms at adhesion sites. So far we have thrown light on a number of adhesion-inhibiting mechanisms including those of Lactobacillus kitasatonis,which suppresses the cellular attachment of Salmonella; Lactobacillus reuteri,which inhibits the adhesion to receptors of Helicobacter pylori,a bacterium suggested to cause stomach cancer; and Lactobacillus gasseri,which arrests the adhesion to cells of the food poisoning bacteria Campylobacter jejuni.In addition, because of the problem of drug-resistant bacteria, we are also looking for new antimicrobial agents produced by lactic acid bacteria.

8. Conclusion: Probiotics and Agromedicine

Lactic acid bacteria and bifidobacteria play the leading probiotic roles, and it has been shown that the probiotic effects of these bacteria are dependent on the bacterial strain. This makes it necessary, for example, to develop efficient screening methods to find strains with useful functions. Nevertheless, such efforts and the development of probiotics for human use will make no progress in illuminating probiotic functions without the cooperation of researchers in the field of medical science. On the research level, agriculture?medicine collaboration has already achieved considerable progress, and that collaboration will probably grow stronger. The Kitasato University School of Medicine and the School of Veterinary Medicine's Department of Animal Science are considering providing agromedical education starting the next academic year, which would be the first such attempt in Japan. They are now discussing content, and they plan to offer some items with probiotics as the subject matter because probiotics are thought to be the best subject to link food/environment with medicine.　

1)Fuller R., Probiotics in man and animals. J. Appl. Bacteriol. 66,365-378(1989).
2)Mitsuoka T., Significance of dietary modification of intestinal flora and intestinal environment. Bioscience Microflora 19, 15-25(2000).

1. Introduction

If you say "foods that are good for your health", I think many people will think of "health foods". But there are considerable doubts about how good for you these health foods really are. In truth, there have been not a few stories about people who suffered health damage because of health foods. A study by the Japanese Ministry of Health, Labour and Welfare (MHLW) released August 2008 found that pharmaceutical ingredients whose unauthorized sale is banned by the Drugs, Cosmetics and Medical Instruments Act were detected in 15% of health foods that made claims of physical invigoration. A 2005 study by the Tokyo Metropolitan Government found that 85% of the health foods on the market either violated or were suspected of violating laws covering their labeling and advertising (Drugs, Cosmetics and Medical Instruments Act; Law to Prevent Excessive Premiums and Unreasonable Representations; JAS Law; and Health Promotion Law).,br> At the same time, many people have certain expectations for the efficacy of supplements and other health foods. In a recent private study (subjects were 500 men and women aged 50?79), 48.8% said they "ordinarily take supplements", and of those, 87.3% said they "take them every day". Probably there are also many people who eat health foods while feeling some doubts about them. Here I would like to offer some ideas for discussing health foods and functional foods, asking what capabilities we can expect of them and to what extent (possibilities and limitations).　

2. Are Health Foods Necessary?

When asked at a forum "Are health foods really necessary?", Dr. Keizo Umegaki of the National Institute of Health and Nutrition replied, "I don't think most people need them".
Dr. Akira Murakami at Kyoto University says, "Many people use health foods because they're lazy, and many people who depend on health foods are cheap."
I too have doubts about using health foods that are too convenient, and I think that in the first place it is above all else important to consider the issue of "food and health" in terms of one's overall dietary lifestyle. Expressed simply with that in mind, my idea is "health foods are unnecessary, but functional foods are necessary". We often hear the term "functional foods", and I will explain this important term in the next section.　

3. Health Foods and Functional Foods

I am a functional foods researcher, and it grieves me to have functional foods and health foods put in the same pigeonhole. Unfortunately, however, many people think of them as more or less the same thing. The following diagram shows how I see in my mind the relationships of ordinary foods, health foods, functional foods, foods for specified health uses, and pharmaceuticals.

But when adding legal circumstances, no clear distinction can be made between health foods and functional foods. I want readers to see the difference between health foods and functional foods as the presence or absence of scientific basis. While the government view of health foods is "broadly, foods in general that are sold and used as foods which contribute to the maintenance and improvement of health", this has no scientific basis. As things stand now many health foods are "foods which merely give the impression of health". Herein we find the reason that I want to make a distinction between health foods and functional foods. I should add that foods for specified health uses may be considered functional foods that have met a number of conditions and have legal approval (as of August 31, 2008, 797 items had permission to be labeled as such).

4. "Food and Health" for What Purpose?

The health food market is currently seen to be about \1.6 trillion. Supplements alone account for about \700 billion. The over-the-counter drug market (cold remedies, digestive medicines, eyedrops, tonics, vitamins, and others) is about \610 billion, which is arguably quite large. About 10 years ago the OTC drug market was approaching \1 trillion, but in 2005 it yielded first place to foods for specified health uses.
This was big news to the parties concerned. One cannot deny that market appeal (size and growth promise) was one reason for the appearance of many dubious health foods, but recent household finance surveys indicate that consumer health food expenditures have peaked, and there are whispers that the market has expanded to its limit. I hope this will be for the best by leading to the elimination of inferior health foods and the development of excellent functional foods.
The media too have all covered "food and health". Of course, this is because of viewers' and readers' needs, but it seems that especially television has created some programs merely as a way of bolstering ratings. Even if viewers might see them as "informational programs" and use the information with gratitude, if producers make them as "variety programs" without serious thought, the result is tragic. TV programs are very influential, and I strongly sense the presence of TV such as when taking questions after lectures to the general public. Although considerable caution has been exercised since the "white kidney bean incident" (where almost 160 people were struck with vomiting and diarrhea after following a weight-loss plan involving white kidney beans that was broadcast by a major TV network in Japan), there are concerns about what people do once they forget the pain.
Although I have strayed a bit from my subject, it appears that current problems involving health foods arose in part because the industry and the media have not always treated the matter of "food and health" with sincerity.　

5. Foods for Special Dietary Uses Too Are Functional Foods

The appearance of "hypoallergenic rice" (low-allergen rice) was no doubt very good news for people with rice allergies. This rice was put on sale in 1993 by Shiseido with the product name "Fine Rice"; as the first food for specified health uses, it is a functional food that also has historical significance. Fine Rice is now positioned not as a food for specified health uses, but as a "food for ill people" within the category of "foods for special dietary uses". Some of the categories of foods for special dietary uses established by law are "foods for ill people", "powdered milk for pregnant and nursing women", "infant formula", and "foods for the elderly". As of March 2008, 505 such foods have been authorized.
Foods for the ill and other foods for special dietary uses have a somewhat special position as functional foods, and there is a very great need for them. I myself was involved in the development of foods for those with difficulty chewing and swallowing (foods for the elderly), and I think that the development of such foods has great social significance.　

6. Dietary Lifestyle and Nutritional Education

In 2007, much discussion arose around a book (Boushoku no Jidai, Fusosha Publishing) which recounted the story of an elementary school child who said matter-of-factly, "I chewed gum for breakfast". While a bit hard to believe, it is apparently not unusual to hear about such things on school campuses. This is perhaps not unrelated to the trend in which adults take the easy route toward nutrition by depending on health foods. Although there are pros and cons with the Basic Law on Nutritional Education, which entered into force in 2005, the current situation perhaps requires the government to now consider dietary lifestyles.
At the First Agromedicine Symposium (March 10, 2006) Professor Yoshiharu Aizawa, dean of our School of Medicine, delivered a talk entitled "Agromedicine as Seen from Medical Science". In that talk he emphasized the need for nutritional education and said, "I perceive the need to encompass not only 'food' but the entirety of 'food and eating', and to systematize conventional food science as food and eating science". While there is great significance in functional foods, considering "dietary lifestyle in its entirety" always takes precedence, and that is one of the major goals of agromedicine. At the Second Agromedicine Symposium (October 13, 2006) Professor Tomiharu Manda of our School of Veterinary Medicine delivered a talk titled "Conservation Livestock Farming ? From Production to the Hospital" in which he described how safe, worry-free beef raised on 100% farm-grown pasture at the Kitasato University Yakumo Farm is used in meals given to patients in Kitasato University Hospital. Professor Manda remarked, "Here we can see the collaboration of agriculture, the environment, and medicine". Efforts underway at Yakumo Farm are communicated to citizens through public lectures and other means, which could also be seen as nutritional education activities conducted by Kitasato University.　

7. Scientific Basis and Communication to Consumers

A scientific basis to establish the healthful effects of functional foods is needed in order to clearly differentiate them from products merely portraying themselves as health foods. At the First Agromedicine Symposium, Professor Takafumi Kasumi of the Nihon University College of Bioresource Sciences emphasized "nutrigenomics and tailor-made foods" in a talk called "Human Health and Functional Foods". Comprehensive analyses using DNA microarrays to examine the effects of food constituents on gene expression are now frequently conducted, and it seems we have made a certain amount of progress in understanding the relationships between food functions and scientific evidence. I am exploring the function analysis of peptides formed by the breakdown of food proteins, and their applications in food. I have incorporated analyses using DNA microarrays, and the results look very promising.
Despite progress in technologies to obtain a scientific basis, one feels the limits of functional foods in the difficulty of communicating the science to consumers. At present, a few functional foods are authorized to have certain effects and benefits listed on their labels because they have obtained permits from the MHLW as foods for specified health uses. However, for functional foods other than those for specified health uses, there is no way to use the data that scientists have gone to the trouble of assembling. Because some foods are hard to approve as foods for specified health uses, it seems we need something more than the "foods for specified health uses" system.
Manufacturers take great pains in naming and labeling their products in consideration of the Drugs, Cosmetics and Medical Instruments Act and other related laws and notifications from the MHLW. Nevertheless, product concepts are not necessarily communicated well to consumers; some products invite misunderstanding, and in some cases give people dubious impressions. I do not agree that the system should be more complicated, but the present system still needs more work. The "foods for specified health uses" system became effective in 1993, and in 2001, the "food with health claims" system was launched. This further brought into existence "foods with nutrient function claims", but very few consumers understand these terms correctly.
Incidentally, one often sees foods labeled "patent pending" or "patented", but in many cases, we do not know what exactly is or will be patented. Additionally, the "revised examination criteria for novelty and inventiveness" issued in recent years by the Japanese Patent Office make it hard for the "invention of use" of functional foods to be recognized, and they are an impediment to developing functional foods.　

8. Some Thoughts on Pet Food Development

Prompted by a request for advice from a graduate who was working for a pet food company, a few years ago I started research on pet food. Fortunately, I obtained the cooperation of many people, won a large competitive research grant from the Japnanese Ministry of Agricuture, Forestry and Fisheries, and successfully developed peptide pet food ingredients. For the details (in Japanese), please see the website http://foodpeptide.comof the university-originated venture company Food Peptide Co., Ltd. founded in conjunction with this work.
Humans will sometimes eat foods that "although taste bad appear to be healthful", but pet food that tastes bad will be a commercial failure because pets will not eat it. And even if one replaces a product with a new functional pet food, pet owners will not continue buying it unless some change is manifested. It seems to me that in some ways pet food is, more than human food, chosen according to matter-of-course criteria. I think that "delicious and healthful" is the basis for both functional human foods and functional pet foods. Perhaps it will be possible to apply our experiences in pet food development to human food.

9. Conclusion: The Importance of Collaboration

This has been a somewhat broad-ranging paper, but I hope it will serve to spur thought on "food and health". Due in part to my own lack of ability, I was unable to delve into the real "possibilities and limitations" of functional foods, but I think I was able to provide ideas for discussion.
Because this is a symposium on the collaboration of agriculture and medicine, I would like to close with an appeal for the importance of collaboration. Without agriculture?medicine collaboration, there can be no fundamental approach to the issue of food and health. Functional food research and development also require industry?academia?government collaboration. I am employed by a university, and have benefited greatly from collaboration with graduates. I intend to continue carefully fostering those relationships. And needless to say, interaction with the public (consumers) through public lectures and other events is to us a valuable opportunity for collaboration.