Part 33 (2/2)

35. 35. Sylvia Westphal, ”DNA Nan.o.b.a.l.l.s Boost Gene Therapy,” May 12, 2002, /news/news.jsp?id=ns99992257. Sylvia Westphal, ”DNA Nan.o.b.a.l.l.s Boost Gene Therapy,” May 12, 2002, /news/news.jsp?id=ns99992257.

36. 36. L. Wu, M. Johnson, and M. Sato, ”Transcriptionally Targeted Gene Therapy to Detect and Treat Cancer,” L. Wu, M. Johnson, and M. Sato, ”Transcriptionally Targeted Gene Therapy to Detect and Treat Cancer,” Trends in Molecular Medicine Trends in Molecular Medicine 9.10 (October 2003): 42129. 9.10 (October 2003): 42129.

37. 37. S. Westphal, ”Virus Synthesized in a Fortnight,” November 14,2003, /news/news.jsp?id=ns99994383. S. Westphal, ”Virus Synthesized in a Fortnight,” November 14,2003, /news/news.jsp?id=ns99994383.

38. 38. G. Chiesa, ”Recombinant Apolipoprotein A-I(Milano) Infusion into Rabbit Carotid Artery Rapidly Removes Lipid from Fatty Streaks,” G. Chiesa, ”Recombinant Apolipoprotein A-I(Milano) Infusion into Rabbit Carotid Artery Rapidly Removes Lipid from Fatty Streaks,” Circulation Research Circulation Research 90.9 (May 17, 2002): 97480; P. K. Shah et al., ”High-Dose Recombinant Apolipoprotein A-I(Milano) Mobilizes Tissue Cholesterol and Rapidly Reduces Plaque Lipid and Macrophage Content in Apolipoprotein e-Deficient Mice,” 90.9 (May 17, 2002): 97480; P. K. Shah et al., ”High-Dose Recombinant Apolipoprotein A-I(Milano) Mobilizes Tissue Cholesterol and Rapidly Reduces Plaque Lipid and Macrophage Content in Apolipoprotein e-Deficient Mice,” Circulation Circulation 103.25 (June 26, 2001): 304750. 103.25 (June 26, 2001): 304750.

39. 39. S. E. Nissen et al., ”Effect of Recombinant Apo A-I Milano on Coronary Atherosclerosis in Patients with Acute Coronary Syndromes: A Randomized Controlled Trial,” S. E. Nissen et al., ”Effect of Recombinant Apo A-I Milano on Coronary Atherosclerosis in Patients with Acute Coronary Syndromes: A Randomized Controlled Trial,” JAMA JAMA 290.17 (November 5, 2003): 22922300. 290.17 (November 5, 2003): 22922300.

40. 40. A recent phase 2 study reported ”markedly increased HDL cholesterol levels and also decreased LDL cholesterol levels,” M. E. Brousseau et al., ”Effects of an Inhibitor of Cholesteryl Ester Transfer Protein on HDL Cholesterol,” A recent phase 2 study reported ”markedly increased HDL cholesterol levels and also decreased LDL cholesterol levels,” M. E. Brousseau et al., ”Effects of an Inhibitor of Cholesteryl Ester Transfer Protein on HDL Cholesterol,” New England Journal of Medicine New England Journal of Medicine 350.15 (April 8, 2004): 150515, content.nejm.org/cgi/content/abstract/350/15/1505. Global phase 3 trials began in late 2003. Information on Torcetrapib is available on the Pfizer site: /are/investors_reports/annual_2003/review/p2003ar14_15.htm. 350.15 (April 8, 2004): 150515, content.nejm.org/cgi/content/abstract/350/15/1505. Global phase 3 trials began in late 2003. Information on Torcetrapib is available on the Pfizer site: /are/investors_reports/annual_2003/review/p2003ar14_15.htm.

41. 41. O. J. Finn, ”Cancer Vaccines: Between the Idea and the Reality,” O. J. Finn, ”Cancer Vaccines: Between the Idea and the Reality,” Nature Reviews: Immunology Nature Reviews: Immunology 3.8 (August 2003): 63041; R. C. Kennedy and M. H. Shearer, ”A Role for Antibodies in Tumor Immunity,” 3.8 (August 2003): 63041; R. C. Kennedy and M. H. Shearer, ”A Role for Antibodies in Tumor Immunity,” International Reviews of Immunology International Reviews of Immunology 22.2 (MarchApril 2003): 14172. 22.2 (MarchApril 2003): 14172.

42. 42. T. F. Greten and E. M. Jaffee, ”Cancer Vaccines,” T. F. Greten and E. M. Jaffee, ”Cancer Vaccines,” Journal of Clinical Oncology Journal of Clinical Oncology 17.3 (March 1999): 104760. 17.3 (March 1999): 104760.

43. 43. ”Cancer 'Vaccine' Results Encouraging,” BBCNews, January 8, 2001, news.bbc.co.uk/2/hi/health/1102618.stm, reporting on research by E. M. Jaffee et al., ”Novel Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor-Secreting Tumor Vaccine for Pancreatic Cancer: A Phase I Trial of Safety and Immune Activation,” ”Cancer 'Vaccine' Results Encouraging,” BBCNews, January 8, 2001, news.bbc.co.uk/2/hi/health/1102618.stm, reporting on research by E. M. Jaffee et al., ”Novel Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor-Secreting Tumor Vaccine for Pancreatic Cancer: A Phase I Trial of Safety and Immune Activation,” Journal of Clinical Oncology Journal of Clinical Oncology 19.1 (January 1,2001): 14556. 19.1 (January 1,2001): 14556.

44. 44. John Travis, ”Fused Cells Hold Promise of Cancer Vaccines,” March 4, 2000, /article.cfm?chanID=sa003&articleID=000C601F-8711-1F99-86FB83414B7F0156. S. Graham, ”Methuselah Worm Remains Energetic for Life,” October 27, 2003, /article.cfm?chanID=sa003&articleID=000C601F-8711-1F99-86FB83414B7F0156.

54. 54. Ron Weiss's home page at Princeton University (/t/technologyreview/may012000/biologicalcomputing. (MayJune 2000), static.highbeam.com/t/technologyreview/may012000/biologicalcomputing.

56. 56. Ibid. See also the list of current research on the MIT Media Lab Web site, /pressreleases/pr042799.html. 5 (May 1999): 45661. For more information on the partners.h.i.+p between Genzyme Transgenics Corporation, Louisiana State University, and Tufts University School of Medicine that produced this work, see the April 27, 1999, press release, ”Genzyme Transgenics Corporation Announces First Successful Cloning of Transgenic Goat,” /pressreleases/pr042799.html.

60. 60. Luba Vangelova, ”True or False? Extinction Is Forever,” Luba Vangelova, ”True or False? Extinction Is Forever,” Smithsonian Smithsonian, June 2003, /smithsonian/issues03/jun03/phenomena.html.

61. 61. J. B. Gurdon and A. Colman, ”The Future of Cloning,” J. B. Gurdon and A. Colman, ”The Future of Cloning,” Nature Nature 402.6763 (December 16, 1999): 74346; Gregory Stock and John Campbell, eds., 402.6763 (December 16, 1999): 74346; Gregory Stock and John Campbell, eds., Engineering the Human Germline: An Exploration of the Science and Ethics of Altering the Genes We Pa.s.s to Our Children Engineering the Human Germline: An Exploration of the Science and Ethics of Altering the Genes We Pa.s.s to Our Children (New York: Oxford University Press, 2000). (New York: Oxford University Press, 2000).

62. 62. As the Scripps Research Inst.i.tute points out, ”The ability to dedifferentiate or reverse lineage-committed cells to multipotent progenitor cells might overcome many of the obstacles a.s.sociated with using ESCs and adult stem cells in clinical applications (inefficient differentiation, rejection of allogenic cells, efficient isolation and expansion, etc.). With an efficient dedifferentiation process, it is conceivable that healthy, abundant and easily accessible adult cells could be used to generate different types of functional cells for the repair of damaged tissues and organs” (mitted cells to multipotent progenitor cells might overcome many of the obstacles a.s.sociated with using ESCs and adult stem cells in clinical applications (inefficient differentiation, rejection of allogenic cells, efficient isolation and expansion, etc.). With an efficient dedifferentiation process, it is conceivable that healthy, abundant and easily accessible adult cells could be used to generate different types of functional cells for the repair of damaged tissues and organs” (/news/news.jsp?id=ns99993208, includes discussion of technical issues. ”Lab Grown Steaks Nearing Menu,” /news/news.jsp?id=ns99993208, includes discussion of technical issues.

68. 68. The halving time for feature sizes is five years in each dimension. See discussion in chapter 2. The halving time for feature sizes is five years in each dimension. See discussion in chapter 2.

69. 69. An a.n.a.lysis by Robert A. Freitas Jr. indicates that replacing 10 percent of a person's red blood cells with robotic respirocytes would enable holding one's breath for about four hours, which is about 240 times longer than one minute (about the length of time feasible with all biological red blood cells). Since this increase derives from replacing only 10 percent of the red blood cells, the respirocytes are thousands of times more effective. An a.n.a.lysis by Robert A. Freitas Jr. indicates that replacing 10 percent of a person's red blood cells with robotic respirocytes would enable holding one's breath for about four hours, which is about 240 times longer than one minute (about the length of time feasible with all biological red blood cells). Since this increase derives from replacing only 10 percent of the red blood cells, the respirocytes are thousands of times more effective.

70. 70. Nanotechnology is ”thorough, inexpensive control of the structure of matter based on molecule-by-molecule control of products and byproducts; the products and processes of molecular manufacturing, including molecular machinery” (Eric Drexler and Chris Peterson, Nanotechnology is ”thorough, inexpensive control of the structure of matter based on molecule-by-molecule control of products and byproducts; the products and processes of molecular manufacturing, including molecular machinery” (Eric Drexler and Chris Peterson, Unbounding the Future: The Nanotechnology Revolution Unbounding the Future: The Nanotechnology Revolution [New York: William Morrow, 1991]). According to the authors: [New York: William Morrow, 1991]). According to the authors: Technology has been moving toward greater control of the structure of matter for millennia....[P]ast advanced technologies-microwave tubes, lasers, superconductors, satellites, robots, and the like-have come trickling out of factories, at first with high price tags and narrow applications. Molecular manufacturing, though, will be more like computers: a flexible technology with a huge range of applications. And molecular manufacturing won't come trickling out of conventional factories as computers did; it will replace factories and replace or upgrade their products. This is something new and basic, not just another twentieth-century gadget. It will arise out of twentieth-century trends in science, but it will break the trend-lines in technology, economics, and environmental affairs. [chap. 1]Drexler and Peterson outline the possible scope of the effects of the revolution: efficient solar cells ”as cheap as newspaper and as tough as asphalt,” molecular mechanisms that can kill cold viruses in six hours before biodegrading, immune machines that destroy malignant cells in the body at the push of a b.u.t.ton, pocket supercomputers, the end of the use of fossil fuels, s.p.a.ce travel, and restoration of lost species. Also see E. Drexler, Engines of Creation Engines of Creation (New York: Anchor Books, 1986). The Foresight Inst.i.tute has a useful list of nanotechnology FAQs (/nano). and (New York: Anchor Books, 1986). The Foresight Inst.i.tute has a useful list of nanotechnology FAQs (/nano). and Nanotechnology Nanotechnology, an online journal (/nanotech/feynman.html. Richard P. Feynman, ”There's Plenty of Room at the Bottom,” American Physical Society annual meeting, Pasadena, California, 1959; transcript at /nanotech/feynman.html.

72. 72. John von Neumann, John von Neumann, Theory of Self-Reproducing Automata Theory of Self-Reproducing Automata, A. W. Burks, ed. (Urbana: University of Illinois Press, 1966).

73. 73. The most comprehensive survey of kinematic machine replication is Robert A. Freitas Jr. and Ralph C. Merkle, The most comprehensive survey of kinematic machine replication is Robert A. Freitas Jr. and Ralph C. Merkle, Kinematic Self-Replicating Machines Kinematic Self-Replicating Machines (Georgetown, Tex.: Landes Bioscience, 2004), /KSRM.htm. (Georgetown, Tex.: Landes Bioscience, 2004), /KSRM.htm.

74. 74. K. Eric Drexler, K. Eric Drexler, Engines of Creation Engines of Creation, and K. Eric Drexler, Nanosystems: Molecular Machinery, Manufacturing, and Computation Nanosystems: Molecular Machinery, Manufacturing, and Computation (New York: Wiley Interscience, 1992). (New York: Wiley Interscience, 1992).

75. 75. See the discussion of nanotube circuitry in chapter 3, including the a.n.a.lysis of the potential of nanotube circuitry in note 9 of that chapter. See the discussion of nanotube circuitry in chapter 3, including the a.n.a.lysis of the potential of nanotube circuitry in note 9 of that chapter.

76. 76. K. Eric Drexler and Richard E. Smalley, ”Nanotechnology: Drexler and Smalley Make the Case for and Against 'Molecular a.s.semblers,' ” K. Eric Drexler and Richard E. Smalley, ”Nanotechnology: Drexler and Smalley Make the Case for and Against 'Molecular a.s.semblers,' ” Chemical and Engineering News Chemical and Engineering News, November 30, 2003, pubs.acs.org/cen/coverstory/8148/8148counterpoint.html.

77. 77. Ralph C. Merkle, ”A Proposed 'Metabolism' for a Hydrocarbon a.s.sembler,” Ralph C. Merkle, ”A Proposed 'Metabolism' for a Hydrocarbon a.s.sembler,” Nanotechnology Nanotechnology 8 (December 1997): 14962, /nanotech/hydroCarbonMetabolism.html. See also Ralph C. Merkle, ”Binding Sites for Use in a Simple a.s.sembler,” 8 (December 1997): 14962, /nanotech/hydroCarbonMetabolism.html. See also Ralph C. Merkle, ”Binding Sites for Use in a Simple a.s.sembler,” Nanotechnology Nanotechnology 8 (1997): 2328, /nanotech/bindingSites.html; Ralph C. Merkle, ”A New Family of Six Degree of Freedom Positional Devices,” 8 (1997): 2328, /nanotech/bindingSites.html; Ralph C. Merkle, ”A New Family of Six Degree of Freedom Positional Devices,” Nanotechnology Nanotechnology 8 (1997): 4752, /nanotech/6dof.html; Ralph C. Merkle, ”Casing an a.s.sembler,” 8 (1997): 4752, /nanotech/6dof.html; Ralph C. Merkle, ”Casing an a.s.sembler,” Nanotechnology Nanotechnology 10 (1999): 31522, /nanotech/casing; Robert A. Freitas Jr., ”A Simple Tool for Positional Diamond Mechanosynthesis, and Its Method of Manufacture,” U.S. Provisional Patent Application No. 60/543,802, filed February 11, 2004, process described in lecture at /Papers/PathDiamMolMfg.htm; Ralph C. Merkle and Robert A. Freitas Jr., ”Theoretical a.n.a.lysis of a Carbon-Carbon Dimer Placement Tool for Diamond Mechanosynthesis,” 10 (1999): 31522, /nanotech/casing; Robert A. Freitas Jr., ”A Simple Tool for Positional Diamond Mechanosynthesis, and Its Method of Manufacture,” U.S. Provisional Patent Application No. 60/543,802, filed February 11, 2004, process described in lecture at /Papers/PathDiamMolMfg.htm; Ralph C. Merkle and Robert A. Freitas Jr., ”Theoretical a.n.a.lysis of a Carbon-Carbon Dimer Placement Tool for Diamond Mechanosynthesis,” Journal of Nanoscience and Nanotechnology Journal of Nanoscience and Nanotechnology 3 (August 2003): 31924, /Nano/JNNDimerTool.pdf; Robert A. Freitas Jr. and Ralph C. Merkle, ”Merkle-Freitas Hydrocarbon Molecular a.s.sembler; in 3 (August 2003): 31924, /Nano/JNNDimerTool.pdf; Robert A. Freitas Jr. and Ralph C. Merkle, ”Merkle-Freitas Hydrocarbon Molecular a.s.sembler; in Kinematic Self-Replicating Machines Kinematic Self-Replicating Machines, section 4.11.3 (Georgetown, Tex.: Landes Bioscience, 2004), pp. 13035, /KSRM/4.11.3.htm.

78. 78. Robert A. Freitas Jr., Robert A. Freitas Jr., Nanomedicine Nanomedicine, vol. 1, Basic Capabilities Basic Capabilities, section 6.3.4.5, ”Chemoelectric Cells” (Georgetown, Tex.: Landes Bioscience, 1999), pp. 15254, /NMI/6.3.4.5.htm; Robert A. Freitas Jr., Nanomedicine Nanomedicine, vol. 1, Basic Capabilities Basic Capabilities, section 6.3.4.4, ”Glucose Engines” (Georgetown, Tex.: Landes Bioscience, 1999), pp. 149-52, /NMI/6.3.4.4.htm; K. Eric Drexler, Nanosystems: Molecular Machinery, Manufacturing, and Computation Nanosystems: Molecular Machinery, Manufacturing, and Computation, section 16.3.2, ”Acoustic Power and Control” (New York: Wiley Interscience, 1992), pp. 47276. See also Robert A. Freitas Jr. and Ralph C. Merkle, Kinematic Self-Replicating Machines Kinematic Self-Replicating Machines, appendix B.4, ”Acoustic Transducer for Power and Control” (Georgetown, Tex.: Landes Bioscience, 2004), pp. 22533, /KSRM/AppB.4.htm.

79. 79. The most comprehensive survey of these proposals may be found in Robert A. Freitas Jr. and Ralph C. Merkle, The most comprehensive survey of these proposals may be found in Robert A. Freitas Jr. and Ralph C. Merkle, Kinematic Self-Replicating Machines Kinematic Self-Replicating Machines, chapter 4, ”Microscale and Molecular Kinematic Machine Replicators” (Georgetown, Tex.: Landes Bioscience, 2004), pp. 89144, /KSRM/4.htm.

80. 80. Drexler, Drexler, Nanosystems Nanosystems, p. 441.

81. 81. The most comprehensive survey of these proposals may be found in Robert A. Freitas Jr. and Ralph C. Merkle, The most comprehensive survey of these proposals may be found in Robert A. Freitas Jr. and Ralph C. Merkle, Kinematic Self-Replicating Machines Kinematic Self-Replicating Machines, chapter 4, ”Microscale and Molecular Kinematic Machine Replicators” (Georgetown, Tex.: Landes Bioscience, 2004), pp. 89144, /KSRM/4.htm.

82. 82. T. R. Kelly, H. De Silva, and R. A. Silva, ”Unidirectional Rotary Motion in a Molecular System,” T. R. Kelly, H. De Silva, and R. A. Silva, ”Unidirectional Rotary Motion in a Molecular System,” Nature Nature 401.6749 (September 9, 1999): 15052. 401.6749 (September 9, 1999): 15052.

83. 83. Carlo Montemagno and George Bachand, ”Constructing Nanomechanical Devices Powered by Biomolecular Motors,” Carlo Montemagno and George Bachand, ”Constructing Nanomechanical Devices Powered by Biomolecular Motors,” Nanotechnology Nanotechnology 10 (1999): 22531; George D. Bachand and Carlo D. Montemagno, ”Constructing Organic/Inorganic NEMS Devices Powered by Biomolecular Motors,” 10 (1999): 22531; George D. Bachand and Carlo D. Montemagno, ”Constructing Organic/Inorganic NEMS Devices Powered by Biomolecular Motors,” Biomedical Microdevices Biomedical Microdevices 2.3 (June 2000): 17984. 2.3 (June 2000): 17984.

84. 84. N. Koumura et al., ”Light-Driven Monodirectional Molecular Rotor,” N. Koumura et al., ”Light-Driven Monodirectional Molecular Rotor,” Nature Nature 401.6749 (September 9, 1999): 15255. 401.6749 (September 9, 1999): 15255.

85. 85. Berkeley Lab, ”A Conveyor Belt for the Nano-Age,” April 28, 2004, /doc.u.ment_display.cfm?section_id=53&doc.u.ment_id=8007, reporting on Tihamer Toth-Pejel, ”Modeling Kinematic Cellular Automata,” April 30, 2004, /doc.u.ment_display.cfm?section_id=53&doc.u.ment_id=8007, reporting on Tihamer Toth-Pejel, ”Modeling Kinematic Cellular Automata,” April 30, 2004, /news/news.jsp?id=ns99994958, reporting on Nadrian Seeman and William Sherman, ”A Precisely Controlled DNA Biped Walking Device,” Jenny Hogan, ”DNA Robot Takes Its First Steps,” May 6, 2004, /news/news.jsp?id=ns99994958, reporting on Nadrian Seeman and William Sherman, ”A Precisely Controlled DNA Biped Walking Device,” Nano Letters Nano Letters 4.7 (July 2004): 12037. 4.7 (July 2004): 12037.

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