In the News: Professional Ethics Report Spring 2015

Chinese Paper on Embryo Engineering Sparks International Debate
by Josh Ettinger

Scientists, policymakers and the general public have long contested the ethics of genetically modifying human embryos, but a recent study in which Chinese researchers used a new method to alter the genes of embryos has reignited the debate.

In a paper published on April 18, 2015 in the open-access journal Protein & Cell, Junjiu Huang and other researchers at Sun Yat-sen University in Guangzhou describe their attempt to use CRISPR/Cas-9 technology to modify genes in human embryos that cause beta thalassemia, a disease that affects 100,000 people worldwide [1, 2]. The researchers used nonviable tripronuclear (3PN) zygotes “because ethical concerns preclude studies of gene editing in normal embryos” [1]. 48 hours after conducting the experiment, only 4 of the 54 modified embryos contained the intended genetic changes. Additionally, the 4 embryos were mosaic, meaning only some of the cells in each contained the desired modifications. There were also a significant number of “off-target” effects or unintended mutations in other genes.

According to Huang, the principal investigator, their research was rejected by Science and Nature on ethical grounds, but both journals have not confirmed whether they received the paper [2]. However, the researchers write that their study was reviewed by their university’s ethics board and complied with international standards [1]. One critic pointed out that as Protein & Cell accepted the paper two days after it was submitted, it most likely was not peer-reviewed [3]. The journal countered the claim, stating that the paper was peer-reviewed on an expedited schedule [4].

The scientific community—including the Chinese researchers—is relatively united in their disapproval of clinical applications of embryo manipulation, but divided on the value of basic research on the method using non-viable embryos [3]. As expressed by ethicists and in the media with movies such as Gattaca, many are concerned about the concept of “designer babies” and the use of genetic engineering to enhance human capabilities beyond normal, which could exacerbate societal inequities and hold other unanticipated consequences.

After rumors about the study circulated a month before its publication, David Baltimore, president emeritus of the California Institute of Technology and 17 co-authors argued in Science that embryonic genetic manipulation should not be conducted until the “…societal, environmental, and ethical implications of such activity are discussed among scientific and governmental organizations” [5]. Other scientists are concerned that the alteration of human embryos would provoke unreasonable criticism of less controversial forms of genetic engineering, which hold promise for fighting cancer and other diseases: “Legitimate concerns regarding the safety and ethical impacts of germline editing must not impede the significant progress being made in the clinical development of approaches to potentially cure serious debilitating diseases” [6]. Jennifer Doudna, a molecular biologist at the University of California, Berkeley, said the Huang experiment was unnecessary because the CRISPR technology is not yet accurate enough for application in humans; it should first be perfected in other systems [3].

In contrast, George Daley, a stem cell biologist at Harvard Medical School, defended the value of basic research into embryonic gene editing, pointing out the benefits of exploring potential risks before clinical applications [3]. Daley added that the researchers complied with international guidelines allowing researchers to experiment with embryonic cells that have not grown for more than 14 days. “[T]o inform any debate on whether this technology could be useful for eradicating disease, one has to understand the range of efficacy and off-target mutagenesis” [3].

In response to the study and the resulting media storm, NIH Director Dr. Francis Collins released a statement reiterating NIH’s stance to not fund research modifying human embryos and noting a Congressional prohibition on funding research that puts human embryos at risk [7]. Furthermore, NIH will not conduct embryonic genetic engineering because of “serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos” [7]. On May 18, 2015, the National Academy of Sciences and National Academy of Medicine announced a plan to hold a summit and develop guidelines on the genetic modification of embryos [8].

[1]http://link.springer.com/article/10.1007%2Fs13238-015-0153-5#page-1
[2] http://ghr.nlm.nih.gov/condition/beta-thalassemia
[3]http://news.sciencemag.org/asiapacific/2015/04/chinese-paper-embryo-engineering-splits-scientific-community
[4]http://news.sciencemag.org/asiapacific/2015/04/journal-responds-controversy-over-embryo-gene-editing-paper
[5]http://www.sciencemag.org/content/348/6230/36.full
[6]http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111
[7]http://www.nih.gov/about/director/04292015_statement_gene_editing_technologies.htm 
[8]http://www.nature.com/news/us-science-academies-take-on-human-genome-editing-1.17581

Director of NIH Issues Statement on Funding for Genomic Editing Technologies
By Priyanka Patel

Francis S. Collins, Director of the National Institutes of Health (NIH), recently released a statement declaring the organization’s opposition towards funding for the use of gene-editing technologies in human embryos.

The statement referred to newly publicized work on gene-editing technology (see previous story). 

Citing issues in safety, ethics, and lack of potential uses of this work, Collins noted that the “alteration of the human germline in embryos for clinical purposes,” though technologically possible, remains a highly contested issue and “has been viewed almost universally as a line that should not be crossed” [1]. It is highly improbable that such research would be allowed in the current legal conditions.

However, the statement also describes the potential uses of and ongoing research in genomic editing and technology funded by the NIH. Projects include the faster development of knockout mouse models of particular diseases, the construction of HIV-1 resistance in human immune cells, and the creation of antimicrobials that defend against dangerous bacteria and viruses.

Above all, Collins emphasized, “well-established scientific and ethical principles” should serve as the foundation for biomedical research and innovation and as a guide for NIH support [1].

[1]http://www.nih.gov/about/director/04292015_statement_gene_editing_technologies.htm

European Commission Responds to European Citizens’ Initiative “Stop Vivisection”
By Carson Martinez

The European Commission (EC) has recently issued a response to the European Citizens’ Initiative (ECI) “Stop Vivisection.” The ECI was created in April of 2012 to promote participatory democracy. It does this by enabling one million Europeans Union (EU) citizens from at least seven EU countries to petition the European Commission to propose legislation on topics where the EU has the authority to legislate. “Stop Vivisection” is an initiative that seeks to reform how biomedical and toxicological research are currently being conducted. Vivisection, the practice of experimenting on live animals for scientific research, has been a topic of discussion long debated in the scientific community. The Initiative is the third of only three ECIs to pass the one million signature threshold to date.  With over 1,170,000 citizen signatures collected, the ECI is hoping to replace animal testing with more precise, consistent human-relevant techniques.

The Initiative urges that the European Union’s Directive 2010/63/EU be rescinded. The directive seeks to improve and protect the welfare of animals required for scientific experimentation by the European Commission. Specifically, the directive outlines the legislation of the “Three R’s”: the requirement to replace, reduce, and refine the role of animals in scientific testing when possible. Proponents hope the abrogation of the directive will change the field of biomedical research for the benefit of animal welfare, the environment, and human kind. The ECI proposes to abolish animal experimentation, and advocates for compulsory use of data directly relevant for human species. The proposal is based on documents that correlate a dramatic rise in many types of illness to the action of chemicals and the inability of the EU to pursue them with the adequate scientific methods of research. In sum, the Initiative stipulates that toxicity testing in animals is more harmful than useful and outlines ten requests directed to the EC in order to phase out animal testing in Europe.

In response, the Commission dismissed the requests and legislative changes proposed by “Stop Vivisection.” The EC stated that it shares the same ultimate goal that animal testing should be eliminated, but its approach will differ from that outlined by the ECI. The EC presently will not issue a ban on animal research as a whole, for fear that it would move biomedical research from Europe to other countries. Although there have been some developments in creating alternative methods that reduce the need for animal testing, certain processes of toxicology and physiology cannot be replaced by such alternatives. Thus, according to the Commission, animal testing is still vital for the protection of human health, animal health, and the environment.

The EC will not repeal directive 2010/63/EU that protects the animals still required for experimentation. Instead, the Commission plans to reduce animal testing by using the directive in order to achieve the fundamental objectives of “Stop Vivisection.” The EC supports the “Three R’s,” while acknowledging the need to accelerate this requirement and continue to fund research to develop alternate approaches to animal testing.

The EC has indicated that it welcomes the participation of citizens in support of animal welfare. The Commission urges the scientific community and the Member States to take into account the requests of “Stop Vivisection” and to participate actively in developing new approaches. The EC will organize a conference by the end of 2016 with the scientific community and relevant stakeholders on phasing out animal testing, where a report will be presented detailing the progress the Commission has made to increase animal welfare and reduce experimentation with animals.

For more information:
The European Citizens’ Initiative
“Stop Vivisection” European Citizens’ Initiative

EPA Opens Draft Action Agenda for Environmental Justice for Public Input
By Priyanka Patel

The Environmental Protection Agency (EPA) recently revealed its Draft EJ 2020 Action Agenda [1] and plan to “advance environmental justice” over the next five years [2]. The draft is now open for comments from interested individuals and organizations. The EJ 2020 Action agenda hopes to engage local and state governments, the public, and stakeholders in its goal to better serve communities through initiatives for environmental justice, with the following goals:

  • “Deepening environmental justice progress in EPA’s programs to improve the health and environment of overburdened communities
  • Collaborating with partners to expand our impact in overburdened communities
  • Demonstrating progress on outcomes that matter to overburdened communities” [2]

These plans include improving regulations to support environmental justice, especially in modes of compliance and enforcement, and creating open channels for public communication and concerns. EPA also plans to collaborate with communities, tribal organizations, local governments, and state agency partners in maintaining community-based projects in health and sustainability. Through the Community Resources Network, EPA hopes to support local efforts in multi-stakeholder engagement and public participation in environmental justice [1].

EPA will demonstrate the progress of these actions through public reports on project development, and allow communities to submit ideas on projects that require attention. Efforts will also be made for community development in climate adaptation and resilience, in addition to greenhouse gas reduction. These initiatives will provide EPA with the opportunity to make a “visible difference in overburdened communities” [1].

Though the plan highlights future tasks and goals, EPA has also committed to sustained efforts for its current projects [2]. These include conversations with numerous stakeholders, including the Interagency Working Group on Environmental Justice, and drafting improved regulations [2].

The draft will be open and available for comment from April 15, 2015 to June 15, 2015 [2]. Written responses should be sent to ejstrategy@epa.gov. EPA also asks that interested parties contact Charles Lee (lee.charles@epa.gov), Deputy Associate Assistant Administrator for Environmental Justice, to obtain further information on these goals or to contribute to dialogue sessions with EPA.

[1]http://www.epa.gov/environmentaljustice/resources/policy/ej2020/draft-framework.pdf
[2]http://www.epa.gov/environmentaljustice/ej2020/