Law, Ethics, Religion, and Clinical Translation in the 21st Century—A Conversation with Il-Hoan Oh

Authors

  • Majlinda Lako Ph.D.,

    Corresponding author
    1. Institute of Human Genetics and NESCI, Newcastle University, International Centre for Life, Central Parkway, Newcastle NE1 3BZ, U.K.
    • Institute of Human Genetics and NESCI, Newcastle University, International Centre for Life, Central Parkway, Newcastle NE1 3BZ, U.K.
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  • Alan Trounson Ph.D.,

    1. Institute of Human Genetics and NESCI, Newcastle University, International Centre for Life, Central Parkway, Newcastle NE1 3BZ, U.K.
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  • Susan Daher Ph.D.

    1. Institute of Human Genetics and NESCI, Newcastle University, International Centre for Life, Central Parkway, Newcastle NE1 3BZ, U.K.
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  • First published online in STEM CELLS EXPRESS October 6, 2010.

About Dr. Il-Hoan Oh

Dr. Oh received his M.D. from the Catholic University of Korea in 1986 and his Ph.D. from the Fels Institute of Molecular Biology and Cancer Research at Temple University, Philadelphia, in 1997. After undertaking a 3-year postdoctoral fellowship at the Terry Fox Lab as a National Institute of Canada Fellow, he returned to Korea to become the Director of the Cell and Gene Therapy Institute at the Catholic University of Korea. Currently, Dr. Oh is Professor and Chairman in the College of Medicine at the Catholic University of Korea, Director of the Catholic High-Performance Cell Therapy Center, and Director of the Korea Stem Cell Therapeutics Evaluation Center.

Dr. Oh is a member of several advisory boards, including the Executive Research and Development Planning Board and the Executive Pharmaceutical Evaluation Committee in Korea, and he sits on the editorial boards of Stem Cells, the International Journal of Hematology, and the Open Transplantation Journal.

“I Believed that as a Physician, I Could Help a Limited Number of Patients, but as a Researcher, I Could Ultimately Help a Much Greater Number of Patients…”

Dr. Oh entered medical school in 1979 and became fascinated by exciting research discoveries such as the description of the double-helix and the pioneering work of Louis Pasteur. “I used to spend my summer vacations in the laboratory performing biochemical research on plasma proteins, and I felt strongly that my efforts in research could help lead to the development of new therapeutic modalities for disease. I believed that as a physician, I could help a limited number of patients, but as a researcher, I could ultimately help a much greater number of patients, in all areas of the world.”1

Figure 1.

Il-Hoan Oh, Professor and Chairman, College of Medicine, Catholic University of Korea.

“After my medical training, I decided to pursue a Ph.D. degree and began my graduate studies in the Fels Institute for Molecular Biology and Cancer Research at Temple University, under the supervision of Dr. Premkumar E. Reddy, a world-leading scientist in the study of oncogenes. I studied the role of the proto-oncogene c-myb in the regulation of hematopoiesis, and this is what naturally led me to become interested in stem cell transplantation. At that time, stem cell transplantation for the regeneration of ablated bone marrow was one of the most exciting areas of medical research. I was very interested in learning more about the molecular mechanisms that regulate the hematopoietic stem cells, and so I joined the Terry Fox Laboratory in Vancouver, Canada as a postdoctoral fellow under the supervision of Dr. Connie Eaves, who was a leader in the field, and in the long-term culture of primary hematopoietic stem cells. My work with Dr. Eaves really sparked my scientific passions, and I realized that the study of hematopoietic stem cells is valuable not only for hematopoietic reconstitution but also could provide a fundamental model to study many types of stem cells.”

“(in Korea)…We Recognized the Need for Stem Cell Therapies to be Appropriately Guided and Regulated…”

“On my return to Korea in 2000, I joined the Stem Cell Research Center at the Catholic University of Korea, which runs the fifth largest stem cell transplantation center in the world. After several years, I had set up my own research lab dedicated to hematopoietic stem cell research combined with the multidisciplinary development of cell therapeutics. I received a governmental core grant and launched Korea's first multidiscipline cell therapy research and development program as well as our High-Performance Cell Therapy Center. We focus on the development of highly efficient stem cell therapeutics that can overcome the current limitations of cell therapy, with researchers working in the fields of hematopoietic stem cell transplantation, vascular regeneration in peripheral limb ischemia and myocardial infarction, neuronal regeneration in cerebral stroke or trauma, stem cell therapy for autoimmune diseases such as rheumatoid arthritis, and stem cell therapy for diabetes. Our center is particularly exciting because it is based on bringing together scientists from various areas of expertise to reach our goals in medical therapeutics.”

“After several years of basic research and clinical trials, we recognized the need for stem cell therapies to be appropriately guided and regulated to ensure both efficient and ethical applications. For patient safety, we must establish detailed guidelines for stem cell therapies. This prompted me to launch research programs for the evaluation of stem cell therapeutics, which is now supported by the Korean Food and Drug Agency (KFDA). Currently in Korea, over 50 stem cell therapies are under clinical investigation. However, much less effort is being invested into studies to address standardization and safety issues. Therefore, with the support of the KFDA, we have recently opened the Korea Stem Cell Therapeutics Evaluation Center, to facilitate these studies and the guidelines for the appropriate development and approval of stem cell therapeutics. As a director of this center, I am working to integrate the efforts of the academic and industrial sectors to facilitate the development of safe and reliable stem cell therapeutics.”

“We Hope That Our Research Will Help Us to Better Utilize Hematopoietic Stem Cells and Their Clinical Applications”

“In my laboratory, we focus on the development of hematopoietic stem cell therapies that can enhance the efficiency of bone marrow regeneration. We have been investigating strategies for co-transplantation of multidonor-derived umbilical cord blood cells with the aid of mesenchymal stromal cells. Using this strategy, a balanced engraftment of stem cells from multiple donors can be achieved. Another interest is in how the microenvironment, or niche, regulates stem cells. Using the structure of the stem cell niche in bone marrow, we are analyzing the cellular signals that can regulate the stem cell niche, which will help us to identify the signals that can target the niche to produce a stimulatory microenvironment for hematopoietic stem cells. One such project in our laboratory is the identification of stroma-mediated wnt/ß-catenin signals that regulate hematopoietic stem cells through the niche; this work was recently published in Stem Cells. What we show in the study is that wnt/ß-catenin signals can cause contrasting biological effects, depending on the target of ß-catenin activation in the microenvironment, and that self-renewal of hematopoietic stem cells is achieved by stromal activation of ß-catenin. This suggests that targeting of the stem cell niche by specific activating signals could serve as a potential therapeutic strategy to activate the efficient regeneration of hematopoietic stem cells. In particular, these kinds of studies on the regulation of the stem cells by the niche will establish a new concept of “crosstalk” disorders, where disorders of the crosstalk between the microenvironment and the stem cells can lead to disorders such as leukemia.”

“In addition, using hematopoietic stem cells as a model, we are also investigating the mechanisms that confer stemness to hematopoietic stem cells. In a very recent study, we characterized the epigenetic signatures that are unique to the undifferentiated state of hematopoietic stem cells, and looked at the dynamics of chromatin structure. Our results suggest that the hierarchy of hematopoietic stem cells can be explained by a hierarchy of epigenetic plasticity. We hope these studies will help us to better manipulate stemness in various types of stem cells.

“We Need to Remember that Ultimately We Are Working to Advance Stem Cell Science to Help People and Our Society”

“Science often moves very quickly, propelled by the excitement and motivation of researchers with each new finding. However, our society generally agrees that scientific development should be monitored and controlled from both a social and an ethical perspective. Stem cell science has raised significant concerns and yet is also viewed as one of most promising potential treatments for all kinds of disease, and it is already being widely sought by patients. This means that we as scientists need to be alert and recognize any issues that could have serious ethical repercussions in our society. I am not saying that we should be afraid of society's opinions but that we need to be aware of the fundamental positions related to these issues.”

“Since the incident involving Dr. Hwang's cloning of human embryos, public awareness of the need for ethical regulations has increased. Korea has enacted specific laws to reinforce biomedical ethics and increase patient safety. As stem cell therapies are still under development and have the potential to be used in many different ways, we are continually seeking to maintain an appropriate level of legislation to ensure that public safety and ethics are not violated, without suppressing important research activities.”

“It Is Very Important that the Public Understands the Process of Scientific Development…”

“In the past, scientists have not been nearly as actively involved in social discussions about the legal and ethical issues related to research as they are now. The involvement of scientists in these discussions is important, as government policies on research are largely determined based on the understanding and support of the society. Scientists should therefore participate from the very early stages of discussions on policy, so that all members of the society can base their views and judgments on the most current facts and truths. Without sufficient participation from scientists, these discussions often tend to be led by groups who do not sufficiently understand the technicalities and realities of the field, and their views can be biased.”

“It is very important that the public understands the process of scientific development, that is, that developments are triggered by fundamental discoveries of scientific principles, which are then used to further expand our knowledge, and to produce new technologies and treatments. This means that there will naturally be a lag between these discoveries and the technological advances. Unfortunately, we have already experienced what can happen when people are not patient enough regarding these scientific developments. It can lead to scientific forgeries, driven by the expectations of producing “great” results, and to people “shopping” for unauthorized stem cell therapies. This phenomenon is being reported all over the world and can severely affect patient safety; hence, they are not validated and monitored. I think that this reveals quite clearly the expense that society pays for their lack of sufficient understanding about the necessary lag between basic research and clinical applications. I believe it is very important that the public have a balanced view about stem cell research, recognizing the exciting advances and need to encourage further study, while still allowing these findings to “ripen” at their own pace.

“Ambitious Young Scientists Are Absolutely Welcome in This Exciting Field”

“I would first point out to young scientists thinking of entering the field that stem cell science is one of the most attractive fields for those who are interested in fundamental basic science as well as its clinical application. Stem cell science is important not only because it can provide therapeutic tools in medical applications but also because it provides a new way of thinking about the most fundamental areas of cell biology, such as cell fate determination, aging, and cell growth. Thus, studying stem cell science is important not only to advance the field of regenerative medicine but also to provide important insights from a new angle into the mechanisms underlying cell behavior, including many kinds of malignant or degenerative disorders. Studying stem cell science means that we are involved in an area of biomedical science with an extensive scope, and we should keep ourselves open to many new horizons. A young scientist determined to enter stem cell research will have to deal with one of the most challenging areas of biomedical science, in terms of both basic and clinical issues, but it is also one of the most promising and exciting fields in science.”

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