Science, Ethics & Policy Issues

Note: article descriptions are taken from abstracts/articles.

Harris, J. (2016). Germline modification and the burden of human existence. The Cambridge Quarterly of Health Care Ethics, 25(1). [in press]

The very idea or intervening in the germline of humans, to modify, if not human nature at least the genetic endowment of some humans, continues to encounter hostility that is unrelated to the expected benefit or to the safety and efficacy of such procedures. To understand the pervasive hostility to the idea of germline modification we need first to look at the roots of this hostility in developments in the 1970’s. In this paper I will not consider issues of safety and efficacy specifically, but will explore the question of whether there exist principled objections to germline modification in general and Mitochondrial Replacement Therapy (MRT) in particular.

Akbari, B.O., Bellen, H.J., Bier, E., Bullock, S.L., Burt, A., Church, G.M., Cook, K.R., Duchek, P., Edwards, O.R., Esvelt, K.M., Gantz, V.M., Golic, K.G., Gratz, S.J., Harrison, M.M., Hayes, K.R., James, A.A., Kaufman, T.C., Knoblich, J., Malik, H.S., Matthews, K.A., O’Connor-Giles, K.M., Parks, A.L., Perrimon, N., Port, F., Russell, S., Ueda, R., Wildonger, J.. (2015). Safeguarding gene drive experiments in the laboratory. Science. Jul 30.

Multiple strategies are needed to ensure safe gene drive experiments.

* Baltimore, D., Berg, P., Botchan, M., Carroll, D., Charo, R. A, Church, G., … Yamamoto, K. R. (2015). A prudent path forward for genomic engineering and germline gene modification. Science, doi: 10.1126/science.aab1028, [epub online ahead of publication].

A framework for open discourse on the use of CRISPR-Cas9 technology to manipulate the human genome is urgently needed. We recommend that steps be taken to:

1) Strongly discourage, even in those countries with lax jurisdictions where it might be permitted, any attempts at germline genome modification for clinical application in humans, while societal, environmental, and ethical implications of such activity are discussed among scientific and governmental organizations. (In countries with a highly developed bioscience capacity, germline genome modification in humans is currently illegal or tightly regulated.) This will enable pathways to responsible uses of this technology, if any, to be identified.

2) Create forums in which experts from the scientific and bioethics communities can provide information and education about this new era of human biology, the issues accompanying the risks and rewards of using such powerful technology for a wide variety of applications including the potential to treat or cure human genetic disease, and the attendant ethical, social, and legal implications of genome modification.

3) Encourage and support transparent research to evaluate the efficacy and specificity of CRISPR-Cas9 genome engineering technology in human and nonhuman model systems relevant to its potential applications for germline gene therapy. Such research is essential to inform deliberations about what clinical applications, if any, might in the future be deemed permissible.

4) Convene a globally representative group of developers and users of genome engineering technology and experts in genetics, law, and bioethics, as well as members of the scientific community, the public, and relevant government agencies and interest groups, to further consider these important issues, and where appropriate, recommend policies.

Cyranoski, D., & Reardon, S. (22 April 2015). Chinese scientists genetically modify human embryos. Nature News.

Rumours of germline modification prove true — and look set to reignite an ethical debate.

Dzau, V. J., & Cicerone, R. J. (2015). Responsible use of human gene-editing technologies. Human Gene Therapy, 26(7), 411-412.

[T]he National Academy of Sciences and the National Academy of Medicine are launching a major initiative to guide decision making about research involving human gene editing. We have appointed a multidisciplinary advisory group that will help steer our initiative. This fall, we will host an international summit to assemble researchers and other experts to explore the scientific, ethical, and policy issues associated with human gene-editing research. In addition, the academies will convene a multidisciplinary, inter-national committee to undertake an in-depth study to examine the scientific underpinnings; clinical implications; and ethical, legal, and social aspects of the use of current and developing human genome editing technologies in biomedical research and medicine.

International Society for Stem Cell Research. (2015). The ISSCR statement on human germline genome modification. Skokie, IL: International Society for Stem Cell Research.

The International Society for Stem Cell Research calls for a moratorium on attempts at clinical application of nuclear genome editing of the human germ line to enable more extensive scientific analysis of the potential risks of genome editing and broader public discussion of the societal and ethical implications.

Ishii, T. (2015). Germline genome-editing research and its socioethical implications. Cell, 21(8), 473-81.

Genetically modifying eggs, sperm, and zygotes (‘germline’ modification) can impact on the entire body of the resulting individual and on subsequent generations. With the advent of genome-editing technology, human germline gene modification is no longer theoretical. Owing to increasing concerns about human germline gene modification, a voluntary moratorium on human genome-editing research and/or the clinical application of human germline genome editing has recently been called for. However, whether such research should be suspended or encouraged warrants careful consideration. The present article reviews recent research on mammalian germline genome editing, discusses the importance of public dialogue on the socioethical implications of human germline genome-editing research, and considers the relevant guidelines and legislation in different countries.

Lander, E. S. (2015). Brave new genome. New England Journal of Medicine, 373, 5-8.

The task now is to develop a clear framework for evaluating human germline editing. Here, Lander, head of the Broad Institute, offers a starting point, focusing on four key issues: technical precision, medical need weighed against potential risks, who has the right to decide, and morality.

* Lanphier, E., Urnov, F., Haecker, S. E., Werner, M., & Smolenski, J. (2015). Don’t edit the human germ line. Nature, 519, 410–411, doi:10.1038/519410a.

In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications. We are concerned that a public outcry about such an ethical breach could hinder a promising area of therapeutic development, namely making genetic changes that cannot be inherited.

National Academies (2015). Advisory Group for Human Gene Editing Initiative Named. News from the National Academies. Retrieved from

The National Academy of Sciences and the National Academy of Medicine have formed an advisory group to counsel the NAS and NAM presidents on their new initiative on human gene editing.  The role of the advisory group will be to identify and gather information and advice from the scientific and medical communities that will enable the academies to guide and inform researchers, clinicians, policymakers, and the public.

National Academies (2015). National Academy of Sciences and National Academy of Medicine Announce Initiative on Human Gene Editing. News from the National Academies. Retrieved from

The National Academy of Sciences and the National Academy of Medicine are launching a major initiative to guide decision making about controversial new research involving human gene editing.  Human gene-editing technologies, such as CRISPR-Cas9, may lead to promising new treatments for disease.  However, recent experiments to attempt to edit human genes also have raised important questions about the potential risks and ethical concerns of altering the human germline.  Future advances are likely to raise new questions.

Nuffield Council on Bioethics. (2015). Genome Editing Working Group Announced. Nuffield Council on Bioethics. Retrieved from See also:

The Council has established a new working group to explore the ethical issues raised by novel genome editing techniques, such as the CRISPR-Cas9 system, that allow precise, targeted changes to be made to DNA molecules in living cells.

Regalado, A. (2015). Engineering the perfect baby. MIT Technology Review. Retrieved from

Scientists are developing ways to edit the DNA of tomorrow’s children. Should they stop before it’s too late?

Sarewitz, D. (2015). Science can’t solve it. Nature. 252, 413-4.

If the sciences of the existential are at hand, then let’s make decisions about them collectively. WWV-type deliberations could address questions about what is acceptable and what isn’t, about appropriate governance frameworks for research, and about the relative priority of different lines of study given ongoing and inevitable uncertainties and disagreements about risks and benefits.

This sort of discussion should continually feed into and set the boundary conditions for expert panels. A truly deliberative process that is geographically distributed and demographically inclusive can reveal the variations in how risks are selected and prioritized in different places and cultures. Values, governance regimes and research agendas can co-evolve in response to such knowledge. Democracy and science will both be better off.

Savulescu, J., Pugh, J., Douglas, T., Gyngell, C. (2015). The moral imperative to continue gene editing research on human embryos. Protein & Cell, 6(7), 476-479.

The publication of the first study to use gene editing techniques in human embryos (Liang et al., 2015) has drawn outrage from many in the scientific community. The prestigious scientific journals Nature and Sciencehave published commentaries which call for this research to be strongly discouraged or halted all together (Lanphier et al., 2015; Baltimore et al., 2015). We believe this should be questioned. There is a moral imperative to continue this research.

Sharma, A., & Scott, C. T. (2015). The ethics of publishing human germline research. Nature Biotechnology, 33(6), 590-592.

The recent furor pertains to worries that germline modifications may be used to produce a living human. Without a clear understanding of the potential risks and benefits, such attempts would be tantamount to unethical human experimentation. We believe, however, that in vitro human germline research will help researchers to reach that understanding. The recommendations published in Science and by the ISSCR do not prohibit in vitro germline research, and we agree with this view.

Society for Developmental Biology. (2015). Position Statement from the Society for Developmental Biology on Genomic Editing in Human Embryos. Retrieved from:

The Board of Directors of the Society for Developmental Biology (SDB) and the Editors of its official journal Developmental Biology are very concerned about the recently published study applying CRISPR/Cas9 genome editing technology to human embryos. SDB supports a voluntary moratorium by members of the scientific community on all manipulation of preimplantation human embryos by genome editing. Such studies raise deep ethical concerns on their own, and in addition could lead to unanticipated consequences if manipulated embryos were implanted into a womb and allowed to develop to term.

Sugarman, J. (2015). Ethics and germline gene editing. EMBO Reports, 16(8), 879-880.

[A]n approach to oversight should have representation from a broad range of stakeholders with legitimate interests and expertise to meaningfully engage in a fair process. While it is unlikely to foster global consensus around all of the inherent issues, having an oversight system in place should help to address and manage the most important concerns and might even lead to generating some globally accepted standards akin to most research with human subjects. Regardless, developing and implementing efficient oversight and policies will require resources and will inevitably raise questions about what, if anything, is exceptional about this sort of research. Unfortunately, existing mechanisms for similar types of oversight—research ethics committees, stem cell oversight committees—do not seem to be appropriately suited to perform review for germline editing, given their composition and operating guidelines. In view of the associated moral stakes, scientific promise and public interest, however, establishing widely accepted approaches toward the oversight of the science seems to be a prudent path forward.

Vogel, G. (2015). Embryo engineering alarm. Science, 347(6228), 1301, doi: 10.1126/science.347.6228.1301

Asilomar. The word conjures up not only stunning California coastline but also vexing questions posed by new, potentially world-changing technologies. In 1975, the Asilomar conference center hosted a meeting where biologists crafted guidelines for research that altered the DNA of living organisms. Now scientists are calling for another Asilomar—this time to discuss the possibility of genetically engineered human beings. In 1975, the notion of using recombinant DNA to design human babies was too remote to seriously consider, but the explosion of powerful new genome-editing technologies such as CRISPR-Cas9, zinc fingers, and TALENs has changed that. They have made it easy for anyone with basic molecular biology training to insert, remove, and edit genes in cells, including sperm, eggs, and embryos, potentially curing genetic diseases or adding desirable traits. Rumors are rife that scientists in China have already used CRISPR on human embryos. Researchers fear that publicity surrounding such experiments could trigger a public backlash that would block legitimate uses of the technology. In two commentaries, one published online in Science on 19 March and one in Nature on 12 March, two groups of scientists recommend what steps the scientific community could take to ensure the technology would be used safely and ethically.

Wade, N. (19 Mar 2015). Scientists seek ban on method of editing the human genome. New York Times. Retrieved from 

Genome Editing: Between Bedside and Bench (companion articles in Nature Medicine):

  • Lombardo, A., & Naldini, L. (2014). Targeted genome editing hits the clinic. Nature Medicine, 20(10), 1101 – 1103, doi:10.1038/nm.3721.
  • Tsai, S. Q., Iafrate, A. J., & Joung, J. K. (2014). Genome editings: a tool for research and therapy: towards a functional understanding of variants for molecular diagnostics using genome editing. Nature Medicine, 20(10), 1103 – 1104, doi:10.1038/nm.3722.
  • Targeted genome editing by engineered endonucleases allows the precise introduction of gene deletions and substitutions into the target genome. In ‘Bench to Bedside’, Keith Joung and his colleagues discuss how genome-editing technologies could be applied to engineer disease-associated somatic variation into human cell lines and disease models. This would allow the functional interpretation of such variants, which could then be applied to molecular diagnostics in the clinic. In ‘Bedside to Bench’, Angelo Lombardo and Luigi Naldini consider the potential applications of genome editing in the clinic, in which engineered endonucleases have been shown to be safe. Endonucleases could replace disease-associated genes with wild-type versions or be used to delete genes encoding receptors essential to viral host entry to prevent infection.

Araki, M., Nojima, K., & Ishii, T. (2014). Caution required for handling genome editing technology. Trends in Biotechnology, 32(5), 234-237.

Genome-editing technology, although a robust tool for genetic engineering, is creating indistinct regulatory boundaries between naturally occurring and modified organisms. However, researchers must act with caution in research and development to avoid misleading society. Furthermore, appropriate regulations should be proactively discussed and established for handling genome-editing technology.

Ishii, T. (2014). Potential impact of human mitochondrial replacement on global policy regarding germline gene modification. Reproductive BioMedicine Online, 29(2), 150-155, doi:10.1016/j.rbmo.2014.04.001.

Previous discussions regarding human germline gene modification led to a global consensus that no germline should undergo genetic modification. However, the UK Human Fertilisation and Embryology Authority, having conducted at the UK Government’s request a scientific review and a wide public consultation, provided advice to the Government on the pros and cons of Parliament’s lifting a ban on altering mitochondrial DNA content of human oocytes and embryos, so as to permit the prevention of maternal transmission of mitochondrial diseases. In this commentary, relevant ethical and biomedical issues are examined and requirements for proceeding with this novel procedure are suggested. Additionally, potentially significant impacts of the UK legalization on global policy concerning germline gene modification are discussed in the context of recent advances in genome-editing technology. It is concluded that international harmonization is needed, as well as further ethical and practical consideration, prior to the legalization of human mitochondrial replacement.

Webber, P. (2014). Does CRISPR-Cas open new possibilities for patents or present a moral maze? Nature Biotechnology, 32, 331-333, doi:10.1038/nbt.2843.

Here, we review the patentability criteria for gene patents and the approaches that patent offices have taken for the patenting of new microorganisms and transgenic plants and animals. We also raise questions about whether the newfound power to make designer plants and animals should be embraced, particularly in light of the rules many national patent offices have against the patenting of “immoral” inventions.

Baruch, S., Huang, A., Pritchard, D., Kalfoglou, A., Javitt, G., Borchelt, R.,  Scott, J., & Hudson, K. (2005). Human germline genetic modification: issues and options for policymakers. Washington, DC: Genetics and Public Policy Center.

This report analyzes the scientific, legal, regulatory, ethical, moral, and societal issues raised by genetic modification of the human germline, provides data about the American public’s views about HGGM, and explores possible policy approaches in this area.