1. Background

On May 3, 1999, President Clinton and Prime Minister Obuchi called for "an expanded dialogue between the United States and Japan on the role of science and technology (S&T) in our societies as we enter the new millennium."  They determined that the two governments would lead deliberations to “consider how advances in science and technology can most effectively contribute to our societies and the global community, and to identify areas in which enhanced bilateral cooperation would be desirable." (See the White House news release in Appendix 1.)  The dialogue was to include representatives from various sectors such as industry, academia, non-governmental organizations and government, who are involved in US-Japan S&T cooperation, with a report of findings due in the spring of 2000.  

1.1. Implementation of the Expanded Dialogue

As a first step, core groups of four persons each were appointed by the US and Japan sides.  The US side was led by Dr. Norman P. Neureiter, retired Vice President of Texas Instruments Asia and currently an industrial consultant, and the Japanese side was led by Professor Hiroo Imura, a physician, former President of Kyoto University and currently Executive Member of the Prime Minister's Council for Science and Technology. Based on two informal meetings and an extended trans-Pacific televideoconference, the core groups selected the specific topics to be taken up in the Dialogue. Subsequently four additional members from each country joined the discussions to complete the 16-member Dialogue Group.  Two formal meetings were convened, first in Washington on February 6-7, 2000 and then in Tokyo on March 10-12.  Group members also conferred with outside advisors in preparing their final submissions. 

1.2. US-Japan S&T Cooperation—A Rich History

The United States and Japan have had an extensive history of scientific and technical cooperation since the end of World War II.  Government agencies in the two countries have sponsored cooperative programs in energy, natural resources, the environment, medicine, earthquakes, space, oceanography, and earth sciences, among others, involving exchanges of information and scientists as well as joint research projects (see the Summary of US-Japan S&T cooperation in Appendix 2).  In addition, a broad range of private-sector joint ventures, alliances, and licensing and supply arrangements exist between US and Japanese corporations in highly technical fields such as chemicals, biotechnology, pharmaceuticals, semiconductors, and computers.  Japan is also home to more US-owned research and development (R&D) facilities than any other country outside the United States, and Japanese companies have more US-based R&D operations than firms of any other nation. 

Beyond the new knowledge that has come from this cooperation, the links between individual scientists and engineers working together across the Pacific toward common goals represent powerful new strands in the fabric that binds our two nations together.  From the perspective of history, that fact alone gives these cooperative relationships a special significance, perhaps of no less import than the science itself.  Our Group strongly endorses the continuation and strengthening of these cooperative ties, and we hope that our recommendations will serve as a guide and a catalyst in that process.   

1.3. Objectives of the Dialogue

Considering the world of the 21st century, it is clear that societies will face many problems in supporting the expected levels of global population at acceptable standards of living.  Although science and technology are often seen as the cause of some of these problems, they are also expected to play a major role in overcoming them.  Our Group believes that individual scientists and engineers should recognize their societal responsibility to contribute to the solution of these problems.  

Furthermore, with the United States and Japan together accounting for more than 60% of global R&D expenditures, our Group believes that our two countries share a responsibility to cooperate in applying S&T resources to solve such problems—some of which derive directly from the widespread application of technology on a global scale.  We feel it is appropriate for the United States and Japan to play a leadership role in these efforts.  As two of the world's most developed and prosperous nations, we also share an interest in fostering international development by working with the developing nations to meet human needs and address problems that impact global well-being.  Accordingly, while we saw our primary our responsibility in the Dialogue to address problems common to the United States and Japan, the universal nature of many of these issues offers opportunity for other nations or international organizations to participate in our joint programs.  

We also recognize, however, that there are many societal problems related to human behavior—ranging from lethal conflict to major health issues—that are better defined in the language of sociology, behavioral sciences, psychology, or even criminology. These issues have been largely neglected in our discussions, not for lack of importance, but because our scientific and technical tools are only beginning to address the complexity of such challenges.  We do, however, strongly support further development of the social sciences and believe that they must play increasing roles in promoting human welfare.  

After considerable discussion, the following criteria were used to select the topics to be treated in our Report: 

• Critical problems of the 21st century

• Directly affecting people's lives and safety

• Of real concern to both the United States and Japan

• Relevant S&T expertise or capacity present in both countries

• Involvement of high quality scientific research

• Potential for multilateral cooperation

As we reflected on the nature of our report and what lasting benefits could derive from our efforts, we set an ambitious goal for our Group.  We have attempted to outline in broad terms a proposed joint research agenda for US-Japan S&T cooperation for the next 5-10 years, aimed toward the solution of some of the critical problems faced by contemporary society. 

Our intent is to focus on actions that can help solve real problems.  While we also recognize budget limitations in both countries, we concluded that it is our job to recommend what we believe should be done—knowing from experience that good ideas will, over time, engender financial support. 

1.4. Science for the Future

Our Group is fully aware of the extensive S&T cooperation that already exists between the United States and Japan.  It is not our intention to discount or supplant those efforts.  Rather, in looking at the challenges of the 21st century, we will stand on the shoulders of those who have gone before, and try to reach further into areas where knowledge gaps still exist, to endorse and promote ongoing efforts of special promise, and to lay out possible new cooperative paths for the future. 

1.4.1. Cooperative Mechanisms

In this connection we would like to make three specific recommendations regarding cooperative mechanisms.  Beyond cooperating on individual projects, we would like to recommend that efforts be made on a selective basis to establish formal, long-term ties between major US and Japanese institutions, that could then focus over a period of years on cooperative programs in specific areas of research.  Such formal ties could facilitate the exchanges of researchers, permit long-term joint planning and complementary use of facilities and scarce resources.  In the private sector, many such arrangements already exist as formal corporate alliances, joint ventures or even mergers and our Committee welcomes these linkages.  However, there would seem to be unrealized potential to build such ties among universities and government laboratories as well. 

The second recommendation is that both countries' R&D funding institutions make special efforts to promote interdisciplinary projects.  Since these projects often involve multiple institutional jurisdictions and different departments of the same or different institutions, administrative barriers can hinder the research work.  Much of cutting-edge science today is being carried out in the spaces between the conventional disciplines, bringing the latest instruments and techniques from many fields to bear on the new problems.  Extra efforts are needed to assure that these multidisciplinary programs can proceed without difficulty. 

The third recommendation refers to the private sector.  Recent changes in Japanese Government policies with respect to foreign direct investment in Japan, as well as deregulation that has begun and is continuing in individual sectors, have opened new opportunities for US business that did not exist a decade ago.  Proactive efforts by Japanese Government organizations such as MITI and JETRO to develop alliances with high tech firms in the United States and to encourage equity ownership in Japanese companies are reflections of this greater openness toward foreign participation in the Japanese economy.  Furthermore, recent Japanese legislation has been aimed at facilitating cooperation between Japanese industry and Japanese university research activities.  This development may also make it possible for US companies to enter into new kinds of cooperative research relationships with Japan. What happens in this area will depend on the responses of US companies to these new opportunities.  Our Dialogue Group believes it is appropriate for the US Government wherever possible to encourage and assist the development of such private, commercial relationships. 

1.5. Structure and Content of the Report

The topics selected by our Dialogue Group are of two types.  First are issues such as health and medicine, environment, energy, freshwater management, natural disaster mitigation, societal aspects of information technology, and new frontiers in science and technology—which can be addressed by research and for which we make specific proposals.  Secondly, topics such as the role of science in policy decision-making, science education and the public understanding of science and technology, and the ethical and social responsibility of scientists and engineers are issues we considered important to the future vitality of science and scientific inquiry in both countries, but not addressable by conventional research programs. 

In these latter areas we have sought agreement among our Dialogue members on certain basic generalities about the relationship between science and society as a whole.  It is our hope that these conclusions might be useful to our governments in the formulation of public policies relating to scientific research and the introduction and use of new technologies.  In some cases, it may be useful for the United States and Japan to play a leadership role in convening bilateral or multilateral conferences for broader consideration of these issues, where final judgments may be conditioned as much by culture as by rational thought. 

In conclusion, we hope that the following discussion of these subjects will be helpful to our governments in addressing some pressing societal problems, in extending the benefits of that work to the developing world, and in further strengthening the US-Japan relationship.

2. Health and Medicine

2.1. Recent Trends

Building on the results of past scientific research, 21st century medicine is poised to understand more fully the basic biological mechanisms of disease and to use this knowledge to develop new methods of effective treatment and prevention. 

Reduction of the burden of disease and premature or excess mortality are subjects of high importance for the developing world and the transition economies.  Continued impoverishment, crowding, and, in some cases, absolute increase in populations, have combined to sustain or even increase the prevalence of certain infectious diseases. Hepatitis C, influenza, tuberculosis and malaria, all life threatening, are difficult or impossible to prevent by immunization, and in most cases, difficult to treat with drugs.  Ever-increasing mobility of citizens across national boundaries guarantees further spread of these conditions.  Additionally complicating this picture is AIDS, a plague of modern society which, in turn, reduces the resistance to other serious infections, especially tuberculosis. 

Among many industrialized nations, pronounced demographic trends of increased longevity and decreased fertility have steadily increased the proportion of elderly citizens, fast bringing new attention to diseases and disabilities of the elderly and a quest for ways to improve not only the length of life but, also, the quality of life.  In the United States, for example, during the 20th century the number of persons under age 65 tripled. At the same time, the number aged 65 or over jumped by a factor of 11.  The "oldest old"—those aged 85 and over—are the most rapidly growing elderly age group. Between 1960 and 1994, their numbers rose 274 percent.  In Japan, the trend of an increasingly elderly population is even more striking: between 1950 and 2000, the ratio of the population aged 15-64 to the population aged 65 and older fell from 12 to 5. 

In light of these recent trends, two areas that merit particular consideration in Japan-US cooperation are infectious diseases and diseases associated with aging.  Both these areas can benefit from a variety of avenues of scientific inquiry including those dealing with the genetic basis for biological phenomena.  One of the most remarkable achievements of the life sciences is sequencing of genomes of human and other living organisms.  Knowledge of the genomes of many pathogenic microbes helps understand how those microbes infect humans, how they cause disease, what determines their virulence, what leads to drug resistance, and which portion of the genome is important for inducing immunity. 

There is great potential in the two countries' continued partnership. The proposals that follow include both ongoing cooperative research activity (already part of an existing US-Japan agreement where additional emphasis or opportunity exists), as well as new, promising areas of inquiry.  Particular weight is given to avenues that may lead to opportunities for prevention of disease or of complications of disease. 

2.2. US-Japan Cooperation—Past and Present

The US-Japan Cooperative Medical Science Program began in 1965 following an agreement between President Johnson and Prime Minister Sato.  This highly productive program was initially focused on infectious disease prevalent in Southeast Asia.  The program includes panels concerned with AIDS, hepatitis, viral diseases, tuberculosis and leprosy, cholera and related diarrheal diseases, acute respiratory infection, parasitic disease, nutrition and environmental mutagenesis and carcinogenesis.  A long-lived and highly productive US-Japan science agreement, the program supports cooperative research and professional exchanges.  The US-Japan Cooperative Cancer Research Program, begun in 1973 and cosponsored by the National Cancer Institute of NIH and the Japan Society for the Promotion of Science, consists of exchanges of investigators and symposia.  In addition, there is an impressive list of ongoing investigator-to-investigator collaborations in a number of medical science areas. 

2.3. Infectious Diseases

The existing US-Japan Cooperative Medical Science Program should be further strengthened to promote research activities in both countries and to encourage research and clinical practice in Asian nations in the field of infectious diseases, particularly for tuberculosis and AIDS.  We recommend the following avenues of research for tuberculosis and AIDS for enhanced and continuing cooperation.

2.3.1. Tuberculosis

Tuberculosis (TB), believed just a few years ago to be waning toward extinction, has emerged in epidemic proportions in Latin America, parts of Asia, and in the Russian federation and Baltic states.  According to the World Health Organization, one-third of the world's population is infected with Mycobacterium tuberculosis, the causative organism for tuberculosis.  TB is the leading infectious cause of death among adults, killing up to 2 million persons every year, and 8 million new cases occur every year with the burden of disease concentrated among poor populations.  The TB epidemic is enormously complicated by an overlay of drug-resistant disease that is substantially more difficult and costly to treat. The WHO estimated that, by 1996, some 50 million persons were already infected with drug-resistant strains of M. tuberculosis. 

There is much further work to be done in order to understand the basic biological behavior of the infecting organism, the factors that determine susceptibility or resistance to drug therapy and the relationship between HIV infection and drug resistance. Current research is also underway toward the development of DNA vaccines and new treatment regimens.

2.3.2. AIDS 

The AIDS epidemic has aroused great concern among health professionals over the last decade.  According to the United Nations, over five million people are infected with the human immunodeficiency virus (HIV) every year, and more than 2 million die; about one-fifth of those dying are children. 

Efforts to develop an effective vaccine have not yet been successful. Researchable questions include mechanism of viral infection, mucosal immunity, mechanism of development of clinical disease, new means of treatment, vaccine development, and behavioral studies important for prevention of infection.

2.4. Age-Associated Diseases

In an aging population, chronic degenerative diseases such as cancer, cardiovascular disease, cerebrovascular disease, diabetes, and neurological degenerative diseases such as Parkinson's and Alzheimer's disease become increasingly prominent. These diseases burden not only patients but also exert a high cost on society as a whole. 

We recommend that work on non-communicable, age-associated diseases focus on preserving or enhancing the quality of life and preventing disease and disability.  There are many diseases in this category, including a variety of cancers, dementing diseases, Parkinson's disease, cerebrovascular disease, coronary heart disease, diabetes mellitus, hyperlipidemia and hypertension. Among them, there are four groups of diseases that we single out for special consideration.

2.4.1. Cancer

Cancer is the number one cause of death in Japan and the number two cause in the United States.  In spite of recent progress in cancer research, the mechanism of carcinogenesis is still not completely understood.  Treatment of cancer of many organ systems is both relatively non-specific and variably effective. Further research can be focused on genetic susceptibility to cancer and use of DNA-based screening methods to characterize cancer in order to design effective treatments and make accurate prognoses.  We strongly endorse the US-Japan Cooperative Cancer Research Program, which, after a review process completed two years ago, started a new format last year.  Further, we recommend that the United States and Japan consider strengthening their partnership in clinical aspects of cancer research.

2.4.2. Dementing Diseases and Parkinson's Disease

Conditions such as Parkinson's and Alzheimer's disease have become increasingly prominent with the demographic shift towards increasing numbers of the elderly.  In the absence of effective prevention or treatment, the increase in the numbers of people with these diseases will come about as a simple consequence of an increase in the size of the population most at risk, namely, those aged 60 years and older.  Etiology and pathogenesis are still elusive in each case, and there are no known measures for prevention.  Recognition of genetic predisposition suggests the potential for identifying high risk individuals or groups through the characterization of genetic material.  Research on new therapeutic measures, including stem cell therapy, should also be pursued.

2.4.3. Cerebrovascular Disease

Incapacity from stroke is a major cause of disability among the elderly.  Prevention of stroke together with reduction of the degree of impairment are of utmost importance.  Subjects for collaborative research hold exciting possibilities for earlier, effective treatment following stroke, salvage of healthy brain tissue and improved therapeutic outcome from the ability to take advantage of both protective therapies, and repair of damaged brain cells after stroke.

2.4.4. Diabetes Mellitus

Diabetes mellitus is increasing in prevalence in all parts of the world.  It is predicted that there will be over 230 million patients by 2010. Diabetes mellitus is the number one cause of blindness in adults and the number one cause of renal insufficiency requiring hemodialysis in many countries.  Of the two major types of diabetes, Type 1 is caused by autoimmune destruction of specific insulin producing cells of the pancreas.  Type 2 diabetes develops through interactions between genetic predisposition and environmental factors.  Studies in genomics, as described below, are expected to identify the affected genes and provide new perspectives for prevention and treatment of the disease. 

2.5. New Initiatives—Exciting Opportunities in Genetic Research

The potential for using the new science of genetics to shape new and improved strategies for disease prevention and management is seen as enormous.  Both infectious disease and diseases associated with aging will benefit from new advances in genetic research. Advances in genetics, including those from the human genome project, will soon revolutionize our understanding of the pathogenesis of the diseases and will open new horizons in the prevention and management of the diseases. 

New and highly efficient techniques have emerged for identifying single nucleotide polymorphisms (SNPs, the slight differences among people’s genetic makeup). These promise new insights into why and which individuals or populations are susceptible or resistant to disease.  Disease is commonly believed to be the result of several factors, both genetic and environmental, and these new techniques are expected to assist in the understanding of the relative contribution of each of these factors leading ultimately to more specific and efficacious avenues of treatment and prevention. 

Since both the United States and Japan are heavily invested in this type of genetic research, we propose a threefold set of projects that explicitly seeks to exploit the new insights and tools in genetics in order to reduce the burden of disease. 

We propose that a meeting of experts in genetics and disease prevention be convened preferably within the year—to coincide with the forthcoming publication of the rough draft of the human genome study—in order to develop a cooperative program based on these topics:

2.5.1. Basic Biological Mechanisms of Disease

This endeavor is essential for the development of effective and specific new interventions for disease for both prevention and treatment.  Specific examples of expected benefits of using genetic insight to derive understanding of biological mechanisms for medicine include: 

(a) Diabetes.  Better understanding of the genetic background of both Type 1 and Type 2 diabetes promises to reveal effective avenues for both prevention and management.

(b) Tuberculosis and AIDS.  Work is proceeding presently on DNA-based vaccines for prevention of the diseases.

(c) Parkinson's Disease.  Current therapy, built around replacement of the hormone, levodopa, is limited as that drug loses its effectiveness with prolongation of treatment. Fuller understanding of the underlying biological mechanisms of Parkinson's disease, expected to come from genetic inquiry, is felt to be essential in order to craft improved medical interventions.

(d) Dementing Disease.  Some subsets of these diseases are caused by mutations of single genes.  In most cases, specific genetic predispositions are not known. Promise of effective treatment will likely be based on this new insight.

2.5.2. Susceptibility and Resistance to Disease

With comparable exposure to infecting organisms or to environmental physical or chemical agents, some persons become affected by clinical disease and some do not.  Determination of what leads to susceptibility is believed to be important in designing strategies for both treatment and prevention.  Genetic insight is recognized as an important step in deriving that understanding.

2.5.3. Combining Genetics and Epidemiological Research for Understanding the Behavior of Disease in Populations

The traditional methodologies of epidemiological research are useful but limited in their sensitivity to detection.  Combining these methodologies in population studies of disease promises to sharpen the acuity and usefulness of these methods.

3. The Environment

3.1. Importance 

The dramatic improvement in the general standard of living for most people in the twentieth century has brought with it a heavy burden on the environment.  Science and technology have not only contributed to creating prosperity, but also offer the best tools for fighting environmental degradation.  Indeed, for most of the developed world, great progress has already been made in improving air quality, raising water quality, and protecting our lands. 

Yet the 21st century brings us new problems—perplexing because of our limited scientific understanding of those problems.  In some cases, there is doubt about whether problems really exist, and in many cases, there is doubt about whether certain choices of “solutions” will turn out to be sound over a generation or more.  The sciences of the environment are young and the range of environmental issues wide, so we hesitate about whether technological answers will be appropriate and effective. 

New concerns are emerging, for example, about global warming, depletion of the ozone layer, and potential dangers from individual, specific chemical pollutants that may be in the environment.  New questions also emerge about the consequences of carbon dioxide from the energy uses that raise our standard of living, the pesticides that provide a year-round supply of healthful fresh fruits and vegetables, the plastics that protect our water and our foods from contamination, and the chemicals that have transformed our world with an astounding array of technologies. 

Questions arise about the unintended consequences of the use of many chemicals, consequences ranging from frank toxicity, which we are relatively well equipped to understand, to the other extreme, namely, the possible effects of low-levels of chemical exposures on the human body or on ecosystems, where there is a high degree of scientific uncertainty. 

In Chapter 9, we discuss the challenge of making public policy decisions in the face of limited scientific understanding. Should we seek minimum risk regardless of the economic tradeoffs or should we use a “weight of scientific evidence” approach to balance risk management options? This is the choice the world is grappling with in a variety of policy areas.  We believe that inputs to societal choices should be based on the “weight of scientific evidence” approach to balancing risk management options, taking into consideration timescales, unknown factors, overall costs, and many other complex issues.  

To focus on a difficult and specific case as a way to apply this approach, we recommend that an emerging policy choice be selected for a collaborative project between the United States and Japan to develop mechanisms that can help us choose the appropriate balance in such decisions.  One issue that is likely to be the focus of near-term policy decisions, yet has only a limited scientific knowledge base, is the issue of endocrine disrupters in the environment. 

3.2. Cooperation between Japan and the United States

Environmental cooperation between our two countries commenced at the 1970 Japan-US Ministerial Conference on Environmental Pollution, which led to the conclusion of the Environmental Cooperation Agreement and the establishment of a Joint Planning and Coordination Committee (JPCC) and a number of panels in 1975. Since the first JPCC meeting in 1976, eleven meetings reviewed environmental policies in our two countries, including information exchange and collaboration among experts.  At the meeting completed on March 2-3 in Washington, DC, both countries exchanged views regarding chemical issues, including sharing information on endocrine disrupters, a possible process to identify common research, and joint sponsorship of a regional workshop in Asia. 

3.3. The Endocrine Disrupter Case in Brief