Opportunities for Research and Development in Japan - Focus on Advanced Cellular Technologies

June 2011

Since the first announcement in 1998 that James Thompson and colleagues were able to clone human embryonic stem cells capable of differentiation into all forms of human tissue, the science of cell biology and stem cell research has demonstrated clear potential for clinical utility to treat human disease. Cellular therapies represent one of the most promising future technologies to treat and potentially cure many serious human diseases. The pace of research and technological breakthroughs have accelerated over the past 20-years and recent technological advances clearly make stem cell treatment a clinical reality.

However, these advancements in the field of stem cell research and regenerative medicine have generated tremendous debate worldwide about the ethical and religious implication of stem cell research. Many countries have implemented restrictive regulations and policies that make such research into regenerative medicine very difficult. These restrictions have also limited academic research in cellular technologies by restricting funding for stem cell research. While, counties such as the United States, Germany, France, the United Kingdom and Japan are considered to be the leading counties scientific research companies in the world; all of these countries except Japan have significant restrictions on stem cell research and limited funding to academic institutions for such programs. These restrictions and the limited academic funding has left a gap in trained scientists with expertise in stem cell and other regenerative medicines.

In Japan, while the government moved quickly to establish legislation and guidelines to regulate human reproductive cloning, the country remained the most permissive with respect to regenerative medicine and stem cell research. The Ministry of Education, Culture, Sports, Science and Technology (MEXT) in 2001 presented guidelines to set standards for the derivation of human embryonic stem cells (hESCs), including regulations on the donation and use of human embryos, was well as the domestic distribution. The most recent revisions to these guidelines in 2009, eliminated the ministry level review but maintained a two-step scientific review process for all hESC protocols. While in the early 2000?s there were restrictions that impeded the development of hESCs, the system has been significantly revised to be one of the most permissive worldwide. Further, in Japan there have been major breakthrough technologies developed, such as induced pluripotent stem cells (iPS cells) that were first published by Takahashi and Yamanaka in 2006. Since this time the government in Japan has moved quickly to reform and rationalize current regulations and guidelines to promote these new technologies and move them towards clinical utility. More importantly the government in Japan has invested heavily in providing grants for hESC and iPS cell technologies as well as support for small venture companies that have been created out of technologies of major research institutions. The result of both the technological capability of Japan's universities, permissive policies and cultural tolerance of stem cell research has lead to an expansion of efforts within both academic and private companies to advance research on regenerative medicines, including stem cell and iPS cell therapies. The Japanese government has also moved to create biotechnology clusters to promote research and development as well as concentrate companies around major academic support institutions. More importantly, these efforts have also resulted in a large talent pool of experienced researchers in the field that can support biotechnology companies in their research and development programs.

Since 1986, Japan as a country has devoted a higher proportion of its gross domestic product (GDP) to research and development than the United States. Japan also ranks among the highest number of patents per capita than any other country in the world. In 2002, the Japanese government set a biotechnology strategy to significantly grow the biotech industry in Japan. To achieve this objective, the government has focused on supporting corporate research and development efforts to translate academic research and innovative discoveries into experienced companies capable of moving the discoveries into clinical practice. To achieve this goal a significant focus of the government is on providing incentives for new research and development centers in biotechnology.

One biotechnology that is of significant focus given the aging population and recent breakthroughs in regenerative medicines is stem cell and iPS cell research. Stem cell research has a long history in Japan and has been strongly supported by the government as one of the priority areas of science since the turn of the 21st century. After the publication of human induced pluripotent stem (iPS) cells in 2007, the Japanese government has made an even stronger effort to boost stem cell research. The swift move was led by explicit support by many leading politicians. As a result, large research projects are now carried out with funding from various ministries including the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and the Ministry of Health, Labor and Welfare (MHLW). There has also been an exceptionally quick move to revise or establish governmental guidelines for stem cell research. To maximize the outcomes of the research, funding and regulatory systems for clinical translation need to undergo further reform and the participation of private companies should be encouraged. It is also necessary to communicate more information to the society and carry out public engagement activities.

The potential for iPS cell technology to accelerate advances regenerative medicine is also well recognized by the Japanese government and academic researchers. While typically academic researchers compete for recognition on new discoveries, the academic community in Japan, with support of the government has rallied behind this amazing discovery and created an organizational structure that focuses each academic institution on specific focused areas to maximize the utilization of resources. This unprecedented approach is lead by Shinya Yamanaka at Kyoto University with support from other major academic institutions and leaders in the field such as Hiromitsu Nakauchi and Koji Eto at University of Tokyo, who in 2009 announced the ability to create human platelets and other hematologic cells from iPS cells derived from mature epithelial cells. Such advances hold promise to not only treat diseases, but to personalize medicine such that patients own cells can be used to derive iPS cells and subsequently differentiate these cells into other needed cell types in the body. More importantly this wealth of research is now resulting in a large number of trained and experienced scientists that can be utilized to support company research and development facilities focused on regenerative medicine.

Thus, at present Japan remains the world leader in regenerative medicine academic research and is moving quickly to capitalize on this scientific advantage by creating a regulatory and financial environment that supports company efforts to advance these technologies into clinical practice. More importantly, Japan?s academic institutions are now infusing significant human resource into the system in the form of trained scientists that have experience and a focus to develop new cell based technologies such as hESC and iPS cells for use in regenerative medicine.

For Biotechnology and Pharmaceutical companies seeking to enter this market the clear hurdles to supporting research and development centers focused on stem cell technologies are the ability to obtain adequate numbers of trained scientists, and that the country has a regulatory and culturally permissive stance on such stem cell based research. Thus, for those companies, Japan is now clearly a focus for initiation of new research and development facilities or to expand existing facilities with stem cell capabilities. The Japanese government also provides significant support to foreign companies seeking to invest in Japan and establish new research and development facilities. Organizations in the government such as the Japanese External Trade Organization (JETRO) are specifically mandated to provide support to companies that are seeking to do business in Japan and invest in new research and development or manufacturing facilities.

Biotechnology and Pharmaceutical companies that are trying to remain competitive and keep up with a growing expansion of cell technologies and capabilities for forced differentiation should look to Japan as one source of technology and talent. It is anticipated that to stay competitive companies will have to have as one of their strategies a research and development center in one of the biotechnology clusters in Japan designed to support these advanced cellular technologies.

Richard E. Lowenthal, MSc MBA
JETRO NA Healthcare Advisor