Stem cell tourism: the challenge and promise of international regulation of embryonic stem cell-based therapies.

• Author: DeRenzo, Lesley N.

Most cells in the human body are committed to fulfilling a single function. In contrast, embryonic stem cells have the ability to become over 200 distinct cell types. Because of this distinctive characteristic, embryonic stem cells hold vast promise to treat a variety of diseases and disorders. Nevertheless, scientific experts concede that substantial advances in basic biology and clinical technique are essential before embryonic stem cells are readily available for clinical use. Despite the lack of safety and efficacy testing in humans, there are clinics around the world charging patients thousands of dollars for embryonic stem cell-based therapy. As a result, scientists have reported instances of patients suffering adverse outcomes after receiving unregulated stem cell-based therapies. Recognizing the global nature of science and medicine, this Note explores various solutions the United Nations can take to regulate the use of embryonic stem cells in clinical practice.

1. INTRODUCTION II. HESC THERAPIES--INSPIRED BY THE PROMISE, RESPECTFUL OF THE CHALLENGE, YET NAVIGATING WITHOUT A REGULATORY ROAD MAP A. The Challenge and Promise of hESC-Based Therapies B. Stem Cell Tourism C. International Regulation 1. Human subjects research 2. A call for international regulations--Past, present, & future III. HESC THERAPIES--A REGULATORY ROAD MAP TO HELP GUIDE JOURNEY A. Leveraging a Binding U.N. Security Council Resolution-- Immediate Action to Protect National Security and the Public Health 1. The binding resolution--Lessons from 9/11 2. Unregulated hESC-based therapies--A threat to peace? B. Implementation of a Non-Binding UN Resolution--Looking For Short Term Direction Outside of Biomedical Regulation C. Codifying the ISSCR Guidelines by Leveraging Principles from Model Treaties 1. ISSCR guidelines 2. Model treaties 3. Using the ISSCR guidelines and model treaties to create international framework for regulating hESC-based therapy 4. Roadblocks to achieving international regulation IV. CONCLUSION APPENDIX A APPENDIX B APPENDIX C APPENDIX D I. INTRODUCTION

   Stem cell-based therapies have existed since 1968 when clinicians performed the first bone marrow transplantation. (1) Thirty years later, Dr. James A. Thomson, Director of Regenerative Biology for the Morgridge Institute for Research, derived the first human embryonic stem cell (hESC) lines (2) from left-over, pre-implantation human embryos (donated to biomedical research). (3) Dr. Thomson theorized that his findings could revolutionize medicine by generating unlimited sources of human cells for transplantation therapies. (4) However, he cautioned that "substantial advances in basic developmental biology" were essential before hESC-based therapies would be ready for clinical applications: Indeed, scientific experts maintain that the only established, stem cell-based treatment in clinical practice is bone marrow transplantation, which incorporates the use of hematopoietic stem cells. (6)

   Once human cellular-based and tissue-based products (7) became available for therapeutic applications, Congress assigned regulatory responsibility of these products to the U.S. Food and Drug Administration (FDA). (8) The FDA identifies a broad spectrum of safety concerns related to hESC-based products for use in human transplantation. (9) More specifically, the FDA asserts that hESCs--and their derivatives--pose the risk for: (i) spontaneous formation of tumors after injection of hESCs into a human subject; (ii) migration of hESCs to a different site in the human body than what was originally intended; and (iii) development of immunogenicity because of the body's reaction to the foreign material expressed from the human proteins on the hESC product. (10)

   Moreover, it is essential that all left-over, pre-implantation embryos donated for clinical applications are screened for infectious diseases. (11) Accordingly, without standardized safety screening of hESCs for infectious diseases, hESC-based therapies pose the risk of transmitting infectious diseases such as Hepatitis B and HIV/AIDS to the recipients. (12) While hESC research has many safety challenges, the FDA states that the goal of facilitating the development of safe and effective hESC-based products is attainable. (13) And, the FDA emphasizes that cooperative, interdisciplinary efforts are essential to ensure patient safety. (14)

   Despite well-documented safety risks, there are clinics throughout the world, and outside of the FDA's jurisdiction, offering unregulated hESC-based therapies. (15) Unregulated clinics increase the probability that vulnerable patient populations receiving these treatments will experience adverse outcomes. (16) The risks of patients suffering harm from unsubstantiated hESC-based treatments are mitigated within the United States, and in other developed countries, because Federal agencies actively regulate against unsafe medical practices. (17) Unfortunately, at this time, there is no international governing body authorized to set and enforce regulations on the use of hESCs in medical practice. (18) Thus, the burden of regulating hESC-based therapies is dependent on the enforcement mechanisms of individual countries. (19)

   As stem cell treatments emerge as a developing area of medical tourism, scientific experts are becoming increasingly concerned with the potential adverse impacts of hESC-based treatments offered without regulatory oversight. (20) Because of this concern, the International Society for Stem Cell Research (ISSCR) issued guidelines targeting "stem cell tourism." (21) The ISSCR's guidelines highlight the need for well-designed clinical trials as an essential element for administering any proposed hESC-based "therapy." (22) While the ISSCR acknowledges a place for investigator-led medical innovation, it does so with the caveat that such interventions must be conducted in line with the ethical obligation to do no harm. (23)

   Although the guidelines advocate for an international framework, they carry no legal force. (24) Moreover, despite the efforts of a well-intentioned international professional society, the guidelines are easily ignored by unregulated clinics. (25)

   Therefore, Part II of this Note examines the promise of hESC-based therapies and highlights the challenges, or potential dangers, of stem cell tourism without an international regulatory framework. Part III explores a range of effective solutions to combat administering unsafe hESC-based therapies. Specifically, this includes the analysis and application of: (i) a binding U.N. Security Council (Security Council) Resolution to effectuate immediate action in the interest of national security and public health; (ii) a resolution outside of the purview of biomedical regulations in which the World Health Organization (WHO) could issue a non-binding resolution; and (iii) model treaties and the codification of key portions of the ISSCR guidelines into the form of a draft treaty.

2. HESC THERAPIES--INSPIRED BY THE PROMISE, RESPECTFUL OF THE CHALLENGE, YET NAVIGATING WITHOUT A REGULATORY ROAD MAP

   Human embryonic stem cells hold vast potential to treat a variety of diseases and disorders. (26) However, scientific experts concede that substantial advances in basic biology and clinical technique are critical before hESCs are readily available for use in clinical applications. (27) Despite the lack of safety and efficacy testing in humans, there are clinics around the world charging patients thousands of dollars for embryonic stem cell-based therapy. (28)

   As a result, patients lured by the promise of novel stem cell treatment have suffered adverse outcomes from unregulated therapies. (29) Many stem cell scientists agree that there is a need for systemic international regulation and oversight of hESC-based therapeutic treatments offered at various clinics around the world. (30)

   1. The Challenge and Promise of hESC-Based Therapies

      Over the past several years, scientists have made significant discoveries regarding the curative potential of hESCs. (31) For example, in 2009, scientists demonstrated in mice that hESC-derived natural killer cells (32) were better at destroying blood cancer and solid tumors (e.g., breast and prostate cancer) than natural killer cells derived from umbilical cord blood. (33) This finding could promote the use of hESC-derived natural killer cells in humans for cancer therapy. (34)

      Studies in mice have also shown the possibility of engineering cardiovascular tissue for transplantation in humans by inducing hESCs to become heart cells. (35) If successful in humans, this therapy could replace damaged heart tissue caused by heart disease. (36) Another study successfully demonstrated that hESC-derived neurons had the capability of repairing damage caused by a stroke in rats. (37) Rats that suffered mobility restrictions with their paws were able to use their paws again normally after transplantation of the hESC-derived human neurons. (38) Scientists hope to one day use this treatment in humans who suffer mobility impairments from stroke. (39)

      Scientists also successfully improved the motor functions of rats with Parkinson's disease by injecting the rats with hESC-derived dopaminergic nerve cells. (40) Unfortunately, the rats developed brain cancer as a result of stem cell treatment. (41) However, if scientists can learn to control the spontaneous cell differentiation that caused the brain cancer in the rats, hESCs may one day be a plausible source of dopaminergic nerve cells for humans suffering from Parkinson's disease. (42)

      While hESC studies demonstrate promising advancements for potential therapies, (43) they are not without significant scientific hurdles and potential risks. (44) For example, several studies have shown that hESC-based therapies can: (i) cause cancer in the host subject through spontaneous differentiation; (ii) induce immunogenicity responses in the host subject because of foreign human...