Gene therapy oversight: Lessons for nanobiotechnology

Journal of Law, Medicine and Ethics

Volumn 37, Issue 4, 2009, Pages 659-684

  Wolf, Susan M ^a   Gupta, Rishi ^b   Kohlhepp, Peter ^c  

^a UNIVERSITY OF MINNESOTA   (United States)

^b UNIVERSITY OF TEXAS AT DALLAS   (United States)

^c UNIVERSITY OF MINNESOTA LAW SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NANOPARTICLE; RECOMBINANT DNA;

ADVISORY COMMITTEE; BIOMEDICAL TECHNOLOGY ASSESSMENT; CONFERENCE PAPER; CONSENSUS; DRUG APPROVAL; FOOD AND DRUG ADMINISTRATION; GENE THERAPY; GENE TRANSFER; GOVERNMENT REGULATION; HEALTH SERVICES RESEARCH; HISTORY; HUMAN; LEGAL ASPECT; LITERATURE; MANAGEMENT; NANOTECHNOLOGY; NATIONAL HEALTH ORGANIZATION; PEER REVIEW; PUBLIC OPINION; TARGETED GENE REPAIR; UNITED STATES;

ADVISORY COMMITTEES; CONSENSUS; DNA, RECOMBINANT; DRUG APPROVAL; GENE THERAPY; GENE TRANSFER TECHNIQUES; GOVERNMENT REGULATION; HISTORY, 20TH CENTURY; HUMANS; NANOPARTICLES; NANOTECHNOLOGY; NATIONAL INSTITUTES OF HEALTH (U.S.); ORGANIZATIONAL CASE STUDIES; PEER REVIEW, RESEARCH; POLICY MAKING; PUBLIC OPINION; REVIEW LITERATURE AS TOPIC; TARGETED GENE REPAIR; TECHNOLOGY ASSESSMENT, BIOMEDICAL; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 76149124009     PISSN: 10731105     EISSN: 1748720X     Source Type: Journal    
DOI: 10.1111/j.1748-720X.2009.00439.x     Document Type: Conference Paper

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37. Id., at 334.
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39. Id.
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49. Id., at 1.
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53. See Id.
54. National Institutes of Health, Recombinant DNA Advisory Committee, Meeting Minutes, September 17-18, 2007, available at http://oba.od.nih.gov/oba/ rac/minutes/RACminutes-09-07.pdf last visited September 10, 2009).
55. Id., at 30.
56. National Institutes of Health, Recombinant DNA Advisory Committee Agenda, 113th Meeting, June 17-18, 2008, available at http://oba.od.nih.gov/oba/RAC/ meetings/Jun2008/June-08Agenda.pdf last visited September 10, 2009).
57. Id., at 3.
58. National Institutes of Health, Recombinant DNA Advisory Committee, Meeting Minutes, June 17-18, 2008, at 20-21, available at http://oba.od.nih.gov/ oba/RAC/meetings/jun2008/RAC-Minutes-06-08.pdf last visited September 10, 2009).
59. Id., at 22.
60. Id., at 23.
61. J. P. Swazey et al., "Risks and Benefits, Rights and Responsibilities: A History of the Recombinant DNA Research Controversy Southern California Law Review 51, no. 6 (1978 1019 1078, at 1021)
62. D. S. Fredrickson, The Recombinant DNA Controversy - A Memoir: Science, Politics, and the Public Interest 1971-1981 (Washington, D.C. : ASM Press, 2001 at 8-9).
63. Swazey et al., supra note 60, at 1021.
64. Id.
65. See Fredrickson, supra note 61, at 8-9; Swazey et al., supra note 60, at 1021. But the reality was that "[no] one could be certain what that combination of genes might do, and the possibilities ranged from nothing at all to some nightmarish version of contagious cancer." M. Rogers, Biohazard (New York: Knopf, 1977): at 37.
66. See Fredrickson, supra note 61, at 9; Swazey et al., supra note 60, at 1021; see also Rogers, supra note 65, at 36-37.
67. Fredrickson, supra note 61, at 9; Swazey et al., supra note 60, at 1021.
68. Fredrickson, supra note 61, at 8-9.
69. Id.; Swazey et al., supra note 60, at 1021.
70. Fredrickson, supra note 61, at 10; Swazey et al., supra note 60, at 1021; see also Rogers, supra note 65, at 38.
71. Swazey et al., supra note 60, at 1022.
72. Fredrickson, supra note 61, at 11.
73. Id.
74. Id., at 12.
75. Id., at 14.
76. Id. "[S]eventy-eight of the ninety-odd participants voted to send a letter of concern to the prestigious National Academy of Sciences." Rogers, supra note 65, at 42.
77. Id., at 14.
78. M. Singer and D. Söll, "Guidelines for DNA Hybrid Molecules Science 181, no. 4105 (1973 1114.
79. Fredrickson, supra note 61, at 15.
80. Fredrickson, supra note 61, at 16; P. Berg et al., "Potential Biohazards of Recombinant DNA Molecules," Science 185, no. 4148 (1974): 303.
81. Swazey et al., supra note 60, at 1024-1025.
82. Fredrickson, supra note 61, at 17.
83. P. Berg et al., "Summary Statement of the Asilomar Conference on Recombinant DNA Molecules Proceedings of the National Academy of Sciences 72, no. 6 (1975 1981 1984, at 1981.
84. Fredrickson, supra note 61, at 18-27.
85. Id.
86. Berg et al., supra note 83, at 1981.
87. Id., at 1981-1982. Biological barriers include (1) "fastidious bacterial hosts unable to survive in natural environments; and (2) nontransmissible and equally fastidious vectors⋯ able to grow only in specified hosts." Id. at 1982.
88. Id.
89. Berg et al., supra note 80, at 303; Fredrickson, supra note 61, at 31-32. NIH had the statutory authority to form the RAC under 42 U.S.C. § 282(b)(6), which stated that the Director of NIH may "establish such technical and scientific peer review groups and scientific program advisory committees as are needed⋯." 42 U.S.C. § 282(b) (6); J. M. Rainsbury, "Biotechnology on the RAC: FDA/NIH Regulation of Human Gene Therapy," Food & Drug Law Journal 55, no. 4 (2000): 575-600, at 576 n.5.
90. Fredrickson, supra note 61, at 33. The first RAC members (by institutional affiliation and expertise) were: NIH Deputy Director for Science, Chair; Yale, molecular genetics; University of Michigan, molecular genetics; University of Alabama, microbiology; Rockefeller University, cell biology; University of Washington, microbiology; University of California at La Jolla, molecular biology; Stanford, molecular biology; Johns Hopkins, molecular biology; Brookhaven National Lab, molecular biology; University of Wisconsin, phage expert; Harvard, molecular biology; Evergreen State College, biology; Scripps Research Foundation, microbiology; Chief of Viral Diseases, National Institute of Allergy & Infectious Diseases; University of Texas, Austin, government/public affairs (added late 1975); and Georgetown University, ethics (added early 1976). Id., at 34.
91. J. Areen, "Regulating Human Gene Therapy West Virginia Law Review 88, no. 2 (1985 153 171, at 156, quoting J. Califano, Governing America: An Insider's Report from the White House and the Cabinet (New York: Simon and Schuster, 1981): at 203.
92. Id., quoting Califano, supra note 93, at 203 (internal quotation marks omitted).
93. Fredrickson, supra note 61, at 36.
94. Id.
95. Recombinant DNA Research Guidelines, 41 Federal Register 27, 902 (July 7, 1976 see Fredrickson, supra note 61, at 39.
96. Fredrickson, supra note 61, at 40.
97. Fredrickson took over as NIH Director on July 1, 1975. The NIH Almanac: Historical Data, available at http://www.nih.gov/about/almanac/historical/ directors.htm last visited September 10, 2009).
98. Fredrickson, supra note 61, at 44; Recombinant DNA Research Guidelines, supra note 96, at 27,902. RAC went through three versions of the guidelines after Asilomar. D. S. Fredrickson, "A History of the Recombinant DNA Guidelines in the United States in J. Morgan and W. J. Whelan, eds., Recombinant DNA and Genetic Experimentation (New York : Pergamon Press, 1979 at 151, available at http://profiles.nlm.nih.gov/FF/B/B/K/C/-/ffbbkc.pdf last visited September 10, 2009) (stating that Fredrickson "could not even have explained the crucial distinctions between Federal guidelines and regulations").
99. Fredrickson, "A History of the Recombinant DNA Guidelines in the United States supra note 99, at 151-152.
100. Fredrickson, supra note 61, at 51.
101. Id., citing Memorandum from Susan K. Feldman to Director, National Institutes of Health, Definition and Procedures Regarding Regulations for Research on Recombinant DNA Molecules: Information (January 13, 1976) (on file with the National Institutes of Health Central Files, Com 4-4-7-1A).
102. Id., at 50.
103. Id., at 51.
104. Fredrickson, supra note 61, at 272.
105. Id., at 272.
106. Id.
107. L. Thompson, "Human Gene Therapy: Harsh Lessons, High Hopes FDA Consumer Magazine 34, no. 4 (2000 19 24, available at http://www.fda.gov/fdac/ features/2000/500-gene.html last visited May 14, 2009).
108. Rainsbury, supra note 90, at 578.
109. Fredrickson, supra note 61, at 272-274; Rainsbury, supra note 90, at 578.
110. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, Splicing Life: A Report on the Social and Ethical Issues of Genetic Engineering with Human Beings (Washington, D.C. : U.S. Government Printing Office, 1982 at 3-5, available at http://bioethics.gov/ reports/past-commissions/splicinglife.pdf last visited September 10, 2009) [hereinafter Splicing Life hereinafter Hearings on Human Genetic Engineering]; Rainsbury, supra note 90, at 578-581.
111. Hearings on Human Genetic Engineering, supra note 114.
112. Rainsbury, supra note 90, at 579.
113. Id., at 579.
114. Office of Technology Assessment, Human Gene Therapy : Background Paper (December 1984 on file with OTA, Washington, D.C.) [hereinafter OTA, Human Gene Therapy]; Rainsbury, supra note 90, at 578-581.
115. OTA, Human Gene Therapy, supra note 118; Rainsbury, supra note 90, at 578-581.
116. OTA, Human Gene Therapy, supra note 118; Rainsbury, supra note 90, at 578-581.
117. -44 Federal Register 17, 844 (1984 Rainsbury, supra note 90, at 578-581; Working Group on a Response to the Splicing Life Report, April 11, 1983. On the evolution from Working Group to Human Gene Therapy Subcommittee, see National Institutes of Health, Office of Science Policy, "Gene Therapy for Human Patients: Information for the General Public," April 1990, available at http://oba.od.nih.gov/rdnarac/racgeneral-public.html last visited May 15, 2009).
118. Rainsbury, supra note 90, at 578-581.
119. Human Gene Therapy Subcommittee, National Institutes of Health Recombinant DNA Advisory Committee, "Points to Consider in the Design and Submission of Human Somatic-Cell Gene Therapy Protocols DNA Technical Bulletin 1, no. 4 (1986 221 242 hereinafter NIH Points to Consider].
120. See Rainsbury, supra note 90, at 577. DHHS had promulgated regulations for oversight of human subjects research. Areen, supra note 92, at 159, citing 45 C.F.R. § 46 (1983). At the heart of the regulations was review by the Institutional Review Board (IRB) at the researcher's home institution.
121. NIH Points to Consider, supra note 123 J. L. Gage, "Government Regulation of Human Gene Therapy Jurimetrics 27, no. 2 (1987 200 218, at 207-209; 50 Federal Register 2,942 (1985).
122. Rainsbury, supra note 90, at 581; T. Friedmann, P. Noguchi, and C. Mickelson, "The Evolution of Public Review and Oversight Mechanisms in Human Gene Transfer Research: Joint Roles of the FDA and NIH," Current Opinion in Biotechnology 12, no. 3 (2001): 304-307, 304.
123. -51 Federal Register 23, 309 (June 26, 1986 "Nucleic acids or viruses used for human gene therapy will be subject to the same requirements as other biological drugs.").
124. U.S. Food and Drug Administration, Center for Drugs and Biologics, "Points to Consider in Human Somatic Cell Therapy and Gene Therapy (1991) Human Gene Therapy 2, no. 3 (1991 251 256 hereinafter FDA Points to Consider Application of Current Statutory Authorities to Human Somatic Cell Therapy Products and Gene Therapy Products, 58 Federal Register 53, 248 253, 301 (October 14, 1993).
125. Id., at 53,249 ("Gene therapy products are defined⋯ as products containing genetic material administered to modify or manipulate the expression of genetic material or to alter the biological properties of living cells. Some gene therapy products⋯ fall within the definition of biological products and are subject to the licensing provisions of the PHS Act, as well as to the drug provisions of the act.").
126. Id., at II (B)(2).
127. Id.
128. U.S. Food and Drug Administration, "Cellular & Gene Therapy Products available at http://www.fda.gov/Biologics-BloodVaccines/ CellularGeneTherapyProducts/default.htm last visited September 10, 2009).
129. Rainsbury, supra note 90, at 582-583.
130. Id.
131. R. A. Merrill, "Gene Therapy, Law, and FDA Role in Regulation in T. H. Murray and M. J. Mehlmann, eds., Encyclopedia of Ethical, Legal, and Policy Issues in Biotechnology, vol. 1 (New York : John Wiley & Sons, 2000 321 329, at 324.
132. Rainsbury, supra note 90, at 582-585; see also Merrill, supra note 140, at 324.
133. See Rainsbury, supra note 90, at 582-585.
134. Id., at 583.
135. Id., at 583-584.
136. A. B. Naumann, "Federal Regulation of Recombinant DNA Technology: Time for a Change High Technology Law Journal 1, no. 1 (1986 61 98, at 71.
137. Rainsbury, supra note 90, at 585.
138. Id.
139. Merrill, supra note 140, at 324.
140. See Rainsbury, supra note 90, at 585-586; see also Merrill, supra note 140, at 324.
141. Rainsbury, supra note 90, at 586.
142. Merrill, supra note 140, at 325.
143. Rainsbury, supra note 90, at 586.
144. Id., at 586.
145. P. D. Noguchi, "From Jim to Gene and Beyond: An Odyssey of Biologics Regulation Food & Drug Law Journal 51, no. 3 (1996 367 373, 369.
146. National Institutes of Health, Recombinant DNA Research: Actions under the Guidelines, 60 Federal Register 20, 726 (April 27, 1995). See also 62 Federal Register 4,782 (January 31, 1997); Noguchi, supra note 154, at 369-370.
147. Noguchi, supra note 154, at 369.
148. Id.
149. See Rainsbury, supra note 90, at 588 ("External pressure on NIH to eliminate the RAC, or at least to streamline RAC's review process, was predicated largely on the assumption that dual FDA/RAC investigation of clinical protocols was a rate-limiting step in the development of novel genetic therapies.").
150. National Institutes of Health, Recombinant DNA Research: Notice of Intent To Propose Amendments to the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines) Regarding Enhanced Mechanisms for NIH Oversight of Recombinant DNA Activities, 61 Federal Register 35, 774 (July 8,1996).
151. Fredrickson, supra note 61, at 286.
152. Friedmann, Noguchi, and Michelson, supra note 126, at 305.
153. Merrill, supra note 140, at 328 (noting that of the 61 comments the NIH received addressing the proposal to eliminate the RAC, 41 were opposed).
154. -62 Federal Register 4, 782 (January 31,1997).
155. Friedman, Noguchi, and Michelson, supra note 126, at 305.
156. Id.
157. -62 Federal Register 59, 032 (October 31, 1997).
158. On FDA authority, see U.S. Food and Drug Administration, supra note 137; see also Merrill, supra note 140, at 322.
159. Merrill, supra note 140, at 328.
160. See NIH Guidelines for Research Involving Recombinant DNA Molecules (April 2002) Appendix M-1-C-4, available at http://oba.od.nih.gov/rdna/nih- guidelines-oba.html last visited September 10, 2009) [hereinafter NIH Guidelines, 2002].
161. L. Smith and J. F. Byers, "Gene Therapy in the Post-Gelsinger Era JONA's Healthcare Law, Ethics, & Regulation 4, no. 4 (2002 104 110, at 104.
162. Id.
163. N. Somia and I. Verma, "Gene Therapy: Trials and Tribulations Nature Reviews Genetics 1, no. 2 (2000 91 99, at 95.
164. D. T. Zallen, "U.S. Gene Therapy in Crisis Trends in Genetics 16, no. 6 (2000 272 275, 274.
165. J. Silberner, "A Gene Therapy Death Hastings Center Report 30, no. 2 (2000 6.
166. See Zallen, supra note 173, at 274.
167. Id. Furthermore, "only 5% (39/691) of observed serious adverse events, including deaths, were ever reported to NIH." Id.
168. Id.
169. See J. J. E. Andriessen and B. Fahlbruch, How to Manage Experience Sharing: From Organizational Surprises to Organizational Knowledge (Amsterdam : Elsevier, 2004 at 299.
170. Zallen, supra note 173, at 274.
171. Rainsbury, supra note 90, at 594.
172. -65 Federal Register 60, 328 (October 10,2000).
173. See Note, "Guiding Regulatory Reform in Reproduction and Genetics Harvard Law Review 120, no. 2 (2006 574 596, 580 (observing that the RAC "serves as a deliberative body for considering novel ethical questions raised by new types of gene transfer research").
174. Friedmann, Noguchi, and Michelson, supra note 126, at 305.
175. Only about 20-30% of submitted protocols are selected for public review. See N. M. P. King, "RAC Oversight of Gene Transfer Research: A Model Worth Extending?" Journal of Law, Medicine & Ethics 30, no. 3 (2002 381 389, at 385.
176. Id.
177. Friedmann, Noguchi, and Michelson, supra note 126, at 306.
178. King, supra note 184, at 385.
179. See Friedmann, Noguchi, and Michelson, supra note 126, at 306.
180. K. Cornetta and F. O. Smith, "Regulatory Issues for Clinical Gene Therapy Trials Human Gene Therapy 13, no. 10 (2002 1143 1149, 1146.
181. See 66 Federal Register 57, 970 (November 19,2001).
182. See Coronetta and Smith, supra note 189, at 1146; see also NIH Guidelines 2002, supra note 169 ("Principal Investigators must submit, in accordance with this section⋯ a written report on: (1) any serious adverse event that is both unexpected and associated with the use of the gene transfer product (i.e., there is reasonable possibility that the event may have been caused by the use of the product; investigators should not await definitive proof of association before reporting such events)."). See also 21 C.F.R. 312.32 (c) (1) (outlining the FDA's SAE reporting requirements).
183. NIH Guidelines, 2002, supra note 169, at Appendix M-1-C-4-b.
184. R. Weiss, "Gene Research Rule Proposed Washington Post, December 13, 2000, at A2.
185. See King, supra note 184, at 385.
186. Id., at 385-386.
187. See 66 Federal Register 4, 688 (January 18,2001).
188. See Andriessen and Fahlbruch, supra note 178, at 301.
189. See, e.g., National Institutes of Health, "Financial Conflicts of Interest and Research Objectivity: Issues for Investigators and Institutional Review Boards OD-00-040, June 2000, available at http://grants2.nih.gov/grants/ guide/notice-files/NOT-OD-00-040.html last visited September 10, 2009).
190. S. M. Kolemainen, "The Dangerous Promise of Gene Therapy available at http://www.actionbioscience.org/biotech/kolehmainen.html last visited September 10, 2009).
191. Id.
192. Cornetta and Smith, supra note 189, at 1144.
193. Id.
194. Id.
195. See 42 U.S.C. § 262 (a).
196. See 21 C.F.R. § 600.3 (s).
197. Cornetta and Smith, supra note 189, at 1145.
198. FDA/CBER, Human Gene Therapy and the Role of the Food and Drug Administration, available at http://www.fda.gov/cber/infosheets/genezn.htm last visited May 22, 2009).
199. Id.
200. Id.
201. FDA/CBER, Gene Therapy Patient Tracking System, Final Document, June 27, 2002, available at http://www.fda.gov/cber/genetherapy/gttrack.htm last visited May 15, 2009).
202. See King, supra note 184, at 385.
203. National Institutes of Health, Office of Science Policy, "Frequently Asked Questions about the NIH Review Process for Human Gene Transfer Trials available at http://oba.od.nih.gov/rdna/rdna-faq.html last visited September 10, 2009).
204. See Id.
205. U.S. Food and Drug Administration, FDA 101: Human Gene Therapy, available at http://www.cardiumthx.com/flash/pdf/genetherapy022608.pdf last visited September 10, 2009).
206. U.S. Food and Drug Administration, "Human Gene Therapy and the Role of the Food and Drug Administration available at http://www.fda.gov/cber/ infosheets/genezn.htm last visited May 15, 2009).
207. E. Marshall, "Second Child in French Trial Is Found To Have Leukemia Science 299, no. 5605 (2003 320, 320.
208. Recombinant DNA Advisory Committee, Meeting Minutes (February 10, 2003 available at http://www4.od.nih.gov/oba/RAC/minutes/RAC-minutes-02-03.pdf last visited November 30, 2006); Marshall, supra note 216, at 320.
209. Marshall, supra note 216, at 320.
210. See K. Cornetta, "Regulatory Issues in Human Gene Therapy Blood Cells, Molecules & Diseases 31, no. 1 (2003 51 56, at 53.
211. Marshall, supra note 216, at 320; Cornetta, supra note 219, at 53.
212. Recombinant DNA Advisory Committee, Minutes of Meeting (February 10, 2003 at 3, available at http://www4.od.nih.gov/oba/RAC/minutes/RAC-minutes-02-03.pdf last visited May 19, 2009).
213. CBS News Online, "Gene Therapy Questions after Woman's Death September 16, 2007, available at http://www.cbsnews.com/stories/2007/09/16/ health/main3265175.shtml?source=RSSattr=Health-3265175 last visited September 10, 2009).
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216. T. Hampton, "Arthritis Gene Therapy Trial Resumes JAMA 299, no. 1 (2008 28.
217. Id.
218. Mastrobattista et al., supra note 7, at 115.
219. Science Daily, supra note 24.
220. U.S. Congress, Office of Technology Assessment, New Developments in Biotechnology - Background Paper: Public Perceptions of Biotechnology (Washington, D.C. : U.S. Government Printing Office, May 1987 at iii [hereinafter OTA, New Developments].
221. Id.
222. Id., at 5.
223. Id., at 4.
224. Id.
225. See Center for Genetics and Society, Detailed Survey Results, 1992 - March of Dimes, available at http://www.genetic-sandsociety.org/article.php?id= 404#1993time last visited September 10, 2009).
226. Center for Genetics and Society, Detailed Survey Results, December 1993 - Time/CNN, supra note 242. See also P. Elmer-Dewitt, "The Genetic Revolution: New Technology Enables Us to Improve on Nature: How Far Should We Go?" Time 143, no. 3 (1994): 46-53.
227. See Center for Genetics and Society, Detailed Survey Results, 1996 - National Center for Genome Resources, supra note 235. See also E. Singer et al., "The Polls-Trends: Genetic Testing, Engineering, and Therapy Awareness and Attitudes," Public Opinion Quarterly 62, no. 4 (1998): 633-664;
228. D. R. J. Macer, "Public Acceptance of Human Gene Therapy and Perceptions of Human Genetic Manipulation Human Gene Therapy 3, no. 5 (1992 511 518, at 514.
229. OTA, New Developments, supra note 229, at 26.
230. Id.
231. Id., at 25.
232. See Center for Genetics and Society, Detailed Survey Results, October 2002 - Genetics and Public Policy Center, supra note 235.
233. See Rainsbury, supra note 90, at 596.
234. In addition to sources discussed below, see, e.g., R. M. Cook-Deegan, "Human Gene Therapy and Congress Human Gene Therapy 1, no. 2 (1990 163 170)
235. J. Areen, "The Greatest Rewards and the Heaviest Penalties," Human Gene Therapy 3, no. 3 (1992): 277-278
236. D. T. Zallen, "Public Oversight Is Necessary if Human Gene Therapy Is To Progress," Human Gene Therapy 7, no. 7 (1996): 795-797
237. T. Friedmann, "Principles for Human Gene Therapy Studies," Science 287, no. 5461 (2000): 2163-2165; Zallen, supra note 173
238. T. F. Kresina, "Federal Oversight of Gene Therapy Research," in T. F. Kresina, ed., An Introduction to Molecular Medicine and Gene Therapy (New York: Wiley-Liss, Inc.: 2001): 303-317
239. S. Baruch et al., Human Germline Genetic Modification: Issues and Options for Policymakers, Genetics and Public Policy Center, Washington, D.C., 2005, available at http://www.dnapolicy.org/images/reportpdfs/HumanGermlineGenetic- Mod.pdf last visited September 10, 2009).
240. Splicing Life, supra note 111, at 82-88.
241. L. Walters and J. G. Palmer, The Ethics of Human Gene Therapy (New York : Oxford University Press, 1997 at 148.
242. Id., at 151.
243. Id., at 147-152.
244. Id., at 151.
245. King, supra note 184.
246. Id., at 386.
247. S. M. Wolf, "Ban Cloning? Why NBAC Is Wrong Hastings Center Report 27, no. 5 (1997 12 15.
248. See, e.g., King, supra note 184, at 381-382.
249. Id.
250. Id.
251. Id.
252. Walters and Palmer, supra note 245, at 151.
253. D. A. Kessler et al., "Regulation of Somatic-Cell Therapy and Gene Therapy by the Food and Drug Administration New England Journal of Medicine 329, no. 16 (1993 1169 1173).
254. Indeed, given differences between IRBs and IBCs, one could argue this is a four-way system. For an article raising concerns over the IBC system, see M. S. Race and E. Hammond, "An Evaluation of the Role and Effectiveness of Institutional Biosafety Committees in Providing Oversight and Security at Biocontainment Laboratories Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 6, no. 1 (2008 19 35.
255. See S. Jasanoff, The Fifth Branch: Science Advisors as Policymakers (Cambridge : Harvard University Press, 1990). See also, e.g., S. P. Croley, "Theories of Regulation: Incorporating the Administrative Process," Columbia Law Review 98, no. 1 (1998): 1-168.
256. See Croley, supra note 259.
257. M. S. Garfinkel et al., Synthetic Genomics: Options for Governance, October 2007, available at http://www.jcvi.org/cms/fileadmin/site/research/ projects/synthetic-genomics-report/synthetic-genomics-report.pdf last visited September 10, 2009).
258. Id., at 42-44.
259. Kessler et al., supra note 257, at 1735.
260. FDA Science Board, Subcommittee on Science and Technology, FDA Science and Mission at Risk, November 2007.
261. Id., at 24, 27.
262. See J. Kuzma et al., "An Integrated Approach to Oversight Assessment for Emerging Technologies Risk Analysis 28, no. 5 (2008 1197 1220, at 1217. The survey is available in the online version of the article. Id.
263. J. Paradise et al., "Developing U.S. Oversight Strategies for Nanobiotechnology: Lessons from Past Oversight Experiences Journal of Law, Medicine & Ethics 37, no. 4 (2009 688 705.
264. See B. C. Karkkainen, "Information as Environmental Regulation: TRI and Performance Benchmarking, Precursor to a New Paradigm?" Georgetown Law Journal 89, no. 2 (2001 257 370, at 287.
265. See A. C. Lin, "Size Matters: Regulating Nanotechnology Harvard Environmental Law Review 31, no. 2 (2007 349 408, at 361.
266. D. M. Bowman and G. A. Hodge, "A Small Matter of Regulation: An International Review of Nanotechnology Regulation Columbia Science & Technology Law Review 8 (2007 1 36, 13.
267. See, e.g., N. Jacobstein, "Foresight Guidelines for Responsible Nanotechnology Development Institute for Molecular Manufacturing, 2006, available at http://www.imm.org/policy/guidelines/ last visited September 10, 2009).
268. See David Hansen, "Nanotech Strategy Chemical & Engineering News 86, no. 9 (2008 29 30.
269. See National Science and Technology Council, Subcommittee on Nanoscale Science, Engineering, and Technology, National Nanotechnology Initiative: Strategy for Nanotechnology-Related Environmental, Health, and Safety Research, February 2008, at 3, available at http://www.ostp.gov/galleries/NSTC/NNI-EHS- Research-Strategy.pdf last visited September 10, 2009).
270. See Id., at 46.
271. Id., at 44.
272. Id.
273. Chemical & Engineering News, "Nanotech Strategy: Prioritizing Federal Efforts for Studying Health and Safety of Nano-materials Evolves available at http://pubs.acs.org/cen/government/86/8609gov2.html last visited September 10, 2009).
274. See G. E. Marchant and D. J. Sylvester, "Transnational Models for Regulation of Nanotechnology Journal of Law, Medicine & Ethics 34, no. 4 (2006 714 725, at 714.
275. See, e.g., Lin, supra note 269, at 351 ("[N]anotechnology poses distinct and serious concerns that warrant legislation specific to the manufacture and use of nanomaterials."); Marchant and Sylvester, supra note 276, at 723 (discussing transnational regulation, and finding that "nanotechnology will likely require its own unique approach").
276. See, e.g., J. C. Davies, "Managing the Effects of Nanotechnology," Woodrow Wilson International Center for Scholars, January 2006, at 10 (while noting that new regulatory frameworks may be needed, describing only how current regulatory law can be applied to nanotechnology); P. J. Tomasco, Note, "Manufactured Nanomaterials: Avoiding TSCA and OSHA Violations for Potentially Hazardous Substances Boston College Environmental Affairs Law Review 33, no. 1 (2006 205 245, at 238.
277. See M. Greenwood, "Thinking Big About Things Small: Creating an Effective Oversight System for Nanotechnology March 2007, at 10, available at http://www.nanotechproject.org/file-download/files/Greenwood%-%20PEN%207.pdf last visited May 15, 2009).
278. See, e.g., Davies, supra note 280, at 10, 12 (demonstrating that both the Toxic Substances Control Act and the Occupational Safety and Health Act are broad enough to apply to nanotechnology); Lin, supra note 267, at 362, 370 (same). The EPA has also specifically addressed how it accommodates nanotechnology. See, e.g., U.S. Environmental Protection Agency, "Nanotechnology under the Toxic Substances Control Act available at http://www.epa.gov/oppt/nano last visited September 10, 2009) (outlining the adequacy of the Toxic Substances Control Act to protect against release of hazardous nanomaterials into the environment); U.S. Environmental Protection Agency, "Nanoscale Materials Stewardship Program," available at http://www.epa.gov/oppt/nano/stewardship.htm last visited September 10, 2009) (describing a program launched in January 2008 inviting participants to voluntarily report use of nanoscale materials in manufacturing).
279. FDA, Nanotechnology: A Report of the U.S. Food and Drug Administration, July 25, 2007, at 4, available at http://www.fda.gov/nanotechnology/taskforce/ report2007.pdf last visited September 10, 2009).
280. Id., at ii.
281. FDA Regulation of Nanotechnology Products, available at http://www.fda.gov/nanotechnology/regulation.html last visited May 15, 2009).
282. Id., at 30.
283. Id., at 32.
284. A. D. Maynard, "Nanotechnology: Assessing the Risks Nano Today 1, no. 2 (2006 22 33, at 32.
285. M. P. Vinardell, "In Vitro Cytotoxicity of Nanoparticles in Mammalian Germ-Line Stem Cell Toxicological Sciences 88, no. 2 (2005 285 286.
286. T. E. Bell, Understanding Risk Assessment of Nanotechnology, at 2, available at http://www.nano.gov/Understanding-Risk-Assessment.pdf last visited September 10, 2009).
287. Maynard, supra note 288, at 24.
288. See Id., at 31 ("[S]pecific information on hazard, exposure, dose, response, and other compartments within risk assessment frameworks is lacking.").
289. J. P. Ryman-Rasmussen et al., "Penetration of Intact Skin by Quantum Dots with Diverse Physicochemical Properties Toæicological Sciences 91, no. 1 (2006 159 165.
290. G. Oberdorster et al., "Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles Environmental Health Perspectives 113, no. 7 (2005 823 839.
291. Maynard, supra note 288, at 27.
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293. Id.
294. See G. Oberdorster et al., "Translocation of Inhaled UIltrafine Particles to the Brain Inhaled Toxicology 16, nos. 6/7 (2004 437 445, at 441; A. Elder et al., "Translocation of Inhaled Ultrafine Manganese Oxide Particles to the Central Nervous System," Environmental Health Perspectives 114, no. 8 (2006): 1172-1178.
295. See A. Maynard and E. D. Kuempel, "Airborne Nanostructured Particles and Occupational Health Journal of Nanoparticle Research 7, no. 6 (2005 587 614.
296. See Z. L. Wang, "Nanostructures of Zinc Oxide Materials Today 7, no. 6 (June 2004 23 33 (illustrating the synthesis of a wide variety of nanostructures from ZnO).
297. See, e.g., D. B. Warheit et al., "Comparative Pulmonary Toxicity Assessment of Single-Wall Carbon Nanotubes in Rats Toxicological Sciences 77, no. 1 (2004 117 125 V. E. Kagan et al., "Nanomedicine and Nanotoxicology: Two Sides of the Same Coin," Nanomedicine: Nanotechnology, Biology and Medicine 1, no. 4 (2005): 313-316.
298. -35 U.S.C. §§ 200-212.