Publications

This is a list of resources for those who are interested in seeking to understand germline intervention. This list contains reports, non-fiction books, and articles on the topic.

Reports

World Health Organization
The Advisory Committee on Health Research, Genomics and World Health Geneva (2002)
This World Health Organization (WHO) report provides an outline of the potential uses and risks of genomics in the healthcare systems of developing countries and the ethical issues involved with carrying out such research. The report also makes public policy recommendations regarding germline intervention under the auspices and jurisdiction of WHO.

Genetics & Public Policy Center
Human Germline Genetic Modification: Issues and Options for Policymakers
May 2005, available at:http://dnapolicy-content.labvelocity.com/pdfs/6/68176.pdf
The Center for Genetics and Society is a nonprofit information and public affairs organization working to encourage responsible uses and effective societal governance of the new human genetic and reproductive technologies. Their report reviews the advancements in germline genetic modification and previews future possibilities. It also provides public opinions on these technologies and stresses the need for policy to address safety and ethical concerns.

President’s Council on Bioethics (U.S.)
Beyond Therapy: Biotechnology and the Pursuit of Happiness
October 2003, available at: http://www.bioethics.gov/reports/beyondtherapy.
The Council examined the current regulation of biotechnologies dealing with assisted reproduction, human genetics, and human embryo research. The report describes and critically assesses the various oversight and regulatory measures that presently govern the relevant biotechnologies and practices.

Australian Law Reform Commission
ALRC 96 Essentially Yours: The Protection of Human Genetic Information in Australia
March 14, 2003, available at: http://www.austlii.edu.au/au/other/alrc/publications/reports/96.
This report was the result of a 2 year inquiry into the ethical, legal and social implications of the “New Genetics” and recommended establishing a Human Genetics Commission of Australia under federal legislation as an independent statutory authority with sufficient resources to fulfill its mission.

Human Genetics Commission (U.K.)
Genes Direct
March, 2003, available at: http://www.hgc.gov.uk/genesdirect/genesdirect_full.pdf.
The Human Genetics Commission (HGC) is the British Government’s independent advisory body on social and ethical issues in human genetics. This report reviews the controls on genetic tests that are sold directly to the public.

Royal Commission on Genetic Modification (New Zealand)
July 27, 2001
available at: http://www.gmcommission.govt.nz/RCGM/rcgm_report.html.
The Royal Commission on Genetic Modification of New Zealand engaged in a 14-month inquiry pursuant to a warrant from New Zealand’s Governor General to report on the “options available to New Zealand to deal with genetic modification, and to advise on appropriate changes to the relevant regulatory and policy arrangements.” Much of this inquiry focused on food and crops. The basic conclusion reached by the Commission was that New Zealand should “keep its options open,” by not completely banning genetic modification, but by making attempts to oversee and regulate it.

Asia-Pacific International Molecular Biology Network Priority Needs Commission Report on the Status of Molecular Biology and Biotechnology in Thailand
2000, available at: http://www.a-imbn.org/Thailand%202000.pdf
This report aims to identify the needs for the development of biotechnology in Asian Pacific Rim countries, and makes recommendations about advancing scientific research knowledge while balancing regional economic and job creation concerns.

Books (Non-fiction)

Denis Alexander and Robert S. White
Science, Faith, and Ethics: Grid or Gridlock?
Hendrickson Publishers, Inc, Peabody (2004)
As scientists and Christians, authors Denis Alexander and Robert White reconcile these often-conflicting perspectives as they assess cloning, stem cell research, germline intervention, and other biotechnologies.

Joel Garreau
Radical Evolution: The Promise and Peril of Enhancing Our Minds, Our Bodies -- and What It Means to Be Human
(Doubleday: New York 2005)
Garreau takes readers on a journey into the future as he interviews scientists and other thinkers grappling with the implications of our newfound knowledge of the genome. The rate of exponential change in technology, he labels "the Curve," he postulates may lead to three alternative future scenarios: a happy ending that he calls the Heaven Scenario, a tragic ending he calls Hell, and a middle scenario called Prevail in which humans survive the technological advances without creating paradise or destroying the Earth.

Francis Fukuyama
Our Posthuman Future: Consequences of the Biotechnology Revolution
(Picador USA: New York 2003)
Fukuyama argues for the regulation of biotechnology on national and international levels and outlines reasons for deep political and ethical concerns regarding the uses of biotechnology, including germline engineering, which threatens human nature and the foundations of democracy.

Sheldon Krimsky and Peter Shorett, eds.
Rights and Liberties in the Biotech Age: Why We Need a Genetic Bill of Rights
(Rowman & Littlefield Publishers: New York 2005)
This is a compilation of writings by prominent university scientists, civil rights lawyers, and public interest activists who bring their perspectives to issues where science and civil liberties meet. This book explores the impact of new genetic technologies on how people define their "personhood" and their basic civil liberties.

Bill McKibben
Enough: Staying Human in an Engineered Age
(Times Books: New York 2003)
McKibben explains the long-term ethical issues involved in germline genetic engineering and argues for a prohibition of germline engineering, based not in a rejection of all biotechnology, but rather as a way to promote human dignity and to avoid reducing human beings to products to be manipulated at the will of those who control genetic resources.

Glenn McGee
The Perfect Baby
Rowman & Littlefield Publishers, Inc., Lanham (2000)
Bioethicist Glenn McGee explains some of the concerns and clarifies some common misunderstandings about genetic engineering while offering his own views on the future of cloning and germline intervention in society.

Lee Silver
Remaking Eden: Cloning and Beyond in a Brave New World
(Oxford University Press: New York 2000)
Silver optimistically considers the impact of germline genetic engineering and related technologies, including the possibilities of creating children with specific characteristics and the potential division of society along genetically-determined class lines.

Deborah L. Spar
The Baby Business
Harvard Business School Publishing Corporation, Boston (2006)
Through assisted reproductive technologies (ART), couples are beginning to be able to "design" their children by selecting specific genetic traits. Deborah Spar investigates the inner workings of the growing ART sector through interviews with scientists and top executives in the industry. She delves into the ethics of a marketplace for human reproduction and explores the legal regulations that should govern such activities.

Gregory Stock
Redesigning Humans: Choosing Our Genes, Changing Our Future
(Mariner Books: Boston 2003)
Stock looks at the newly available and soon-to-be-available genetic technologies to induce germline changes and compares them to assisted reproductive technologies that are now available. He believes that parents, in an effort to provide advantages for their children, will accept germline engineering, and Stock outlines some of the ethical issues at stake in those choices.

Gregory Stock and John Campbell, eds.
Engineering the Human Germline: An Exploration of the Science and Ethics of Altering the Genes We Pass to Our Children
(Oxford University Press: New York 2000)
Based on lectures given at a 1998 symposium, this book presents short articles from a variety of authors, including scientists, ethicists, and others involved in discussions regarding human germline genetic engineering, including the state of the technology and the likelihood of people adopting germline engineering to correct genetic diseases and introduce genetic enhancements into future generations.

Brian Tokar
Redesigning Life?: The Worldwide Challenge to Genetic Engineering
(Zed Books: London 2001)
Tokar examines genetic engineering from an environmental perspective, including the germline engineering of plants and non-human animals. He finds great reason to be cautious about the widespread and virtually unregulated use of these genetic technologies and highlights some efforts to curb the commercialization of germline engineering.

Leroy Walters and Julie Gage Palmer
The Ethics of Human Gene Therapy
Oxford Press: New York 1996
Walters and Palmer examine the science behind somatic and germline engineering and address some of the ethical issues surrounding human genetic engineering, as well as public policy issues regarding the regulation of genetic manipulation.

Articles

Social and Policy Implications
Underlying Technology and Studies of Its Impact

Articles on Social and Policy Implications

Maxwell J. Mehlman and Kirsten M. Rabe
Any DNA to Declare? Regulating Offshore Access to Genetic Enhancement
28 Am.J.L. & Med. 179-213 (2002)
The authors discuss the social and security reasons for regulating genetic enhancement and suggest that the U.S. government should take measures to regulate enhanced individuals, enhancement services, and the international traffic of money, information, equipment and products for genetic enhancement. Methods of possible regulation and the difficulties inherent in their enforcement are evaluated.

Maxwell J. Mehlman
The Law of Above Averages: Leveling the New Genetic Enhancement Playing Field
85 Iowa L. Rev. 517- 593 (2000)
Concerns of inequality and unfairness presented by genetic enhancement are highlighted. The author suggests methods for minimizing these effects through licensing, a lottery system, and regulation of genetic enhancements.

Maxwell J. Mehlman
How Will We Regulate Genetic Enhancement?
34 Wake Forest L. Rev. 671-714 (1999)
Mechanisms for controlling genetic enhancements and regulatory concerns are addressed. The author offers that a complete ban on genetic enhancements would be ineffective because their demand would produce a black market and that control of genetic enhancements would require a combination of both public and private regulatory mechanisms.

John A. Robertson
Genetic Selection of Offspring Characteristics
76 B.U.L. Rev. 421-482 (1996)
Prebirth selection of offspring characteristics is examined from the perspective of reproductive freedom and rights. The author notes that the debates surrounding genetic selection reveal society’s ambivalence toward the status of children as individuals.

Gregory Stock
The Prospects for Human Germline Engineering
Teleopolis, Frankfurt, Germany January 29, 1999, available at: http://www.heise.de/tp/english/inhalt/co/2621/1.html
The technical approaches of germline engineering, research areas for its application, and its ethical challenges are outlined. The author downplays the concern that germline engineering will be limited to the wealthy few and emphasizes that the technology should progress with society’s full engagement through thoughtful and collective consideration of the possibilities and implications.

Articles on Underlying Technology and Studies of its Impact

Kevin R. Smith
Gene Therapy: The Potential Applicability of Gene Transfer Technology to the Human Germline
Int. J. Med. Sci. 1(2): 76-91 (2004)
This article explores the theoretical possibilities of applying gene transfer techniques to human germline modification. These include pronuclear microinjection, retroviral transfer, and microinjection of retroviral vector with the latter holding the most promise. Ultimately, the author concludes that human germline gene therapy remains only a future possibility until gene transfer technology advances
full article

Paul R. Billings, Ruth Hubbard, and Stuart A. Newman
Human Germline Gene Modification: a Dissent
353 Lancet 1873-1875 (1999)
Germline interventions may cause negative biomedical effects, including the upsetting of “sensitive biological equilibria” and, as shown in experiments with mice, the latent expression in later generations of unexpected genetic alterations. In addition, because storing and handling of gametes may inadvertently modify DNA, unintended germline mutations may also result from present reproductive technologies. The authors argue that there is no justifiable need for germline intervention and that modifications purely for enhancement would lead to eugenics.

Richard A. Bowen, Michael L. Reed, Angelika Schnieke, George E. Seidel, Jr., Alexander Stacey, W. K. Thomas, and O. Kajikawa
Transgenic Cattle Resulting from Biopsied Embryos: Expression of c-ski in a Transgenic Calf
50 Biol. Reprod. 664-668 (1994)
Previous methods of producing transgenic cattle were not cost-effective because large numbers of pregnancies, primarily nontransgenic ones, needed to be carried to term to identify the few calves that were transgenic. The authors designed a protocol to identify successful genetic transfer by biopsying calf embryos prior to their implantation, reducing the number of implantations and subsequent pregnancies necessary to produce a transgenic calf.

Anthony W.S. Chan, Kowit-Yu Chong, Christa Martinovich, Calvin Simerly, and Gerald P. Schatten
Transgenic Monkeys Produced by Retroviral Gene Transfer into Mature Oocytes
291 Science 309-312 (2001)
Researchers attempted to create transgenic rhesus monkeys utilizing a retrovirus in order to track germline modifications in subsequent generations, but out of 224 injected egg cells, only one transgenic monkey was born.

Deborah O. Co, Anita H. Borowski, Josephine D. Leung, Jos van der Kaa, Sandra Hengst, Gerard J. Platenburg, Frank R. Pieper, Carl F. Perez, Frank R. Jirik, and Jan I. Drayer
Generation of Transgenic Mice and Germline Transmission of a Mammalian Artificial Chromosome Introduced into Embryos by Pronuclear Microinjection
8 Chromosome Res. 183-191 (2000)
Transgenic mice were produced through pronuclear microinjection of a genetically engineered mammalian artificial chromosome in order to detect whether the artificial chromosome was present in offspring.

Jon W. Gordon
Genetic Enhancement in Humans
283 Science 2023-2024 (1999)
Genetic enhancement in humans would be medically unacceptable at the present time due to philosophical and moral opposition, safety and efficacy concerns, as well as an inability to acquire informed consent because the consequences of modifying the germline are unknown. Even though genetic enhancement studies may never lead to a successful enhancement of a human being, they may nonetheless provide new disease treatment and prevention techniques.

Michael Hagmann
Fertility Therapy May Aid Gene Transfer
284 Science 1097-1098 (1999)
Gene transfers have been attempted in animals using DNA microinjection, which injects foreign DNA into fertilized eggs. Other than in mice, these attempts have not been very successful. As an alternative, intracytoplasmic sperm injection (ICSI), an in vitro fertilization technique, can be used to create germline modifications.

Andreas Hofmann, Barbara Kessler, Sonja Ewerling, Myriam Weppert, Barbara Vogg, Harald Ludwig, Miodrag Stojkovic, Marc Boelhauve, Gottfried Brem, Eckhard Wolf, and Alexander Pfeifer
Efficient Transgenesis in Farm Animals by Lentiviral Vectors
4 EMBO Rep. 1054-1058 (2003)
Because the success rate of gene transfer in higher mammals using DNA microinjection is very low, the authors set out to achieve higher transgenesis rates by using lentiviral vectors for gene transfer in pig embryos. Sixty-five percent of the piglets born expressed the transgene in all tissues, including their germ cells.

Jonathan Knight
Saved by Sperm
New Scientist, May 22, 1999, at 21
The author suggests that the in vitro fertilization technique of intracytoplasmic sperm injection (ICSI) is better than other methods of germline modifications. ICSI allows the foreign transgene to more easily enter the sperm and has a higher rate of transgene expression in resulting animals.

Aya Leder, Paul K. Pattengale, A. Kuo, T. A. Stewart, and Philip Leder
Consequences of Widespread Deregulation of the c-myc Gene in Transgenic Mice: Multiple Neoplasms and Normal Development
45 Cell 485-495 (1986)
The researchers produced a transgenic mouse strain expressing a tumor gene in various tissues. The transgene increases the chances of developing different types of tumors. Tumors did not develop in all the tissues where the gene was expressed, indicating that factors other than the transgene contribute to the development of malignancy.

Carlos Lois, Elizabeth J. Hong, Shirley Pease, Eric J. Brown, and David Baltimore
Germline Transmission and Tissue-Specific Expression of Transgenes Delivered by Lentiviral Vectors
295 Science 868-872 (2002)
Transgenic mice and rats were produced by infecting embryos in vitro with lentiviral vectors delivering the green fluorescent protein (GFP) gene in order to determine whether lentiviruses result in low levels of transgene expression similar to oncoretretroviruses.

Nancy J. Nelson
Faux Chromosomes Hit the Streets, Hold Real Promise for Gene Therapy
89 J. Nat’l Cancer Inst. 908-910 (1997)
A team of Ohio researchers at Case Western Reserve University developed human artificial microchromosomes (HAC). Pieces of human DNA were introduced into a human cell line to create the stable HAC, which are about ten to twenty percent the size of naturally occurring human chromosomes. Although many unanswered questions about HACs remain, they may help the study of gene expression and be used as gene therapy vectors in the future, replacing the problematic viral vector technique.

Anthony C.F. Perry, Teruhiko Wakayama, Hidefumi Kishikawa, Tsuyoshi Kasai, Masaru Okabe, Yutaka Toyoda, and Ryuzo Yanagimachi
Mammalian Transgenesis by Intracytoplasmic Sperm Injection
284 Science 1180-1183 (1999)
Intracytoplasmic sperm injection (ICSI) may be a preferred method of mammalian transgenesis because it does not require the additional cloning steps and special containment facilities of viral protocols.

Gurparkash Singh, Dorothy M. Supp, Claire M. Schreiner, John D. McNeish, H. J. Merker, Neal G. Copeland, Nancy A. Jenkins, S. Steven Potter, and William J. Scott, Jr.
Legless Insertional Mutation: Morphological, Molecular, and Genetic Characterization
5 Genes Dev. 2245-2255 (1991)
Transgenic mice were developed with a mutation causing leglessness as a means to study limb morphogenesis. Test results showing elevated rates of cell death and brain, craniofacial, and limb malformations suggest that multiple genes were modified by the transgenic insertion.

Evelyn Strauss
Cancer-Stalling System Accelerates Aging
295 Science 28-29 (2002)
Research by a team of molecular biologists suggests that a protein that reduces the chances of cancer might actually accelerate aging. Although the mutated mice did not develop fatal tumors, they suffered from premature aging and had shorter life spans than normal mice, suggesting that the protein’s power to limit excessive cell division might also hinder the ability to replenish critical cells.

Deborah L. Stull
Better Mouse Memory Comes at a Price
The Scientist, April 2, 2001, at 21
Transgenic “Doogie” mice, which score higher on memory and learning tests, have been found to be especially sensitive to chronic pain when compared to nontransgenic mice. A study suggests a physiological link between pain sensation and memory in mice, which may have implications for the treatment of memory disorders and management of chronic pain in humans.

Ya-Ping Tang, Eiji Shimizu, Gilles R. Dube, Claire Rampon, Geoffrey A. Kerchner, Min Zhuo, Guosong Liu, and Joe Z. Tsien
Genetic Enhancement of Learning and Memory in Mice
401 Nature 63-69 (1999)
Researchers produced transgenic “Doogie” mice to test whether they could genetically enhance learning and memory. Transgenic and normal mice were subjected to associative emotional memory tests, emotional learning tests through fear extinction, and spatial learning tests. The Doogie mice outperformed the control mice, leading the researchers to believe that genetic enhancement of memory and intelligence is possible in mammals.

Joe Z. Tsien
Building a Brainier Mouse
282 Sci. Am. 62-68 (2000)
One of the researchers that developed the “Doogie” mice reports that a higher amount of protein called the N-methyl-D-aspartate (NMDA) receptor was present in the transgenic mice. The NMDA receptor fortifies the connection between two simultaneously active neurons, and this strengthening is believed to be the foundation for memory and learning. The research indicated that, when compared to control mice, the Doogie mice were better able to form new memory due to their NMDA receptors remaining open for a longer period.

Stuart D. Tyner, Sundaresan Venkatachalam, Jene Choi, Stephen Jones, Nader Ghebranious, Herbert Igelmann, Xiongbin Lu, Gabrielle Soron, Benjamin Cooper, Cory Brayton, Sang Hee Park, Timothy Thompson, Gerard Karsenty, Allan Bradley, and Lawrence A. Donehower
p53 Mutant Mice that Display Early Ageing-Associated Phenotypes
415 Nature 45-53 (2002)
The p53 tumor suppressor was studied by producing mice with deletions in the p53 gene. Although the mutant mice were more resistant to developing tumors than normal mice, the mutant mice suffered from osteoporosis, shorter life spans, lower tolerance of stress, and atrophy of organs.

Feng Wei, Guo-Du Wang, Geoffrey A. Kerchner, Susan J. Kim, Hai-Ming Xu, Zhou-Feng Chen, and Min Zhuo
Enhancement of Inflammatory Pain by Forebrain NR2B Overexpression
4 Nat. Neurosci. 164-169 (2001)
In a later study of “Doogie” mice, researchers at the Washington University School of Medicine used the transgenic mice to determine the effect of forebrain overexpression of N-methyl-D-aspartate (NMDA) receptor subunit NR2B on pain sensitivity. Compared with normal mice, the transgenic mice had elevated sensitivity to persistent pain stimuli indicating that altering the gene that enhanced learning and memory abilities affected pain perception.

Online Resources