“Recalibration” of Embryo Research Guidelines and a Private Meeting on Synthetic Human Genomes

By SAM WU, BS and KEVIN T. FITZGERALD, SJ, PhD

Controversial breakthroughs, newly proposed guidelines, a private meeting of experts, and a lack of engagement mechanisms to include the public.  Article two in a series on emerging biotechnology.

Nature reported that two research teams have sustained human embryos in vitro for twelve to thirteen days, coming closer to the widely used 14-day limit than ever before. A potential benefit of this scientific advance is that researchers may be able to study early human development with “unprecedented precision”; on the other hand, this research once again raises ethical and practical questions of where to set limits on human embryo research. The Ethics Advisory Board of the US Department of Health, Education, and Welfare originally proposed the 14 day limit in 1979. Twelve countries have since encoded this limit into law and others have written it into guidelines, limiting almost all in vitro research to within those first 14-days of development.

Hyun, et al. suggest that the 14-day rule has been successful in our pluralistic society because it provides space for scientific inquiry and advancement, but also takes into consideration other views that stress the moral status of human embryos. In other words, the rule’s success is due to the fact that it protects the two chief goals that any rule covering human embryo research should uphold: “supporting research and accommodating diverse moral concerns.” The authors further suggest that by viewing established limits in research as “policy tools” rather than as moral truths, “it becomes clear that, as circumstances and attitudes evolve, limits can be legitimately recalibrated.”

The International Society for Stem Cell Research (ISSCR) has attempted to do just that, with the recent release of its updated guidelines on embryonic-stem cell research and clinical translation. The guidelines include several new recommendations, and promote self-regulation of the stem cell research community. One such recommendation suggests that both human embryonic stem cell research and human embryo research undergo review by Embryo Research Oversight committees.  While the ISSCR holds that the 14-day limit remain, it supports more research involving induced pluripotent stem (iPS) cells. Specifically, it recommends that generation of iPS cells be excluded from stem cell research oversight. ISSCR blames incomplete and inaccurate representations of scientific advancements, such as exaggeration of potential benefits and challenges, for public mistrust in science. It, therefore, advocates for improved communication strategies with the public.

Indeed, to “recalibrate” policies regularly in any rapidly advancing field (embryology, genomics, neuroscience, etc.) is good practice. To question current regulations is to create space and opportunity to clarify uncertainties, define goals, evaluate and improve processes, and engage more inclusively. Outcomes of these types of discussions may, in turn, inform ethical policy development that aligns more closely with societal needs and sociocultural contexts at a given time. Hyun et al. call for increased discussion and collaboration in the debate on whether to set a new limit on human embryo research, but like the ISSCR and many others in the field, they place an emphasis on the role and interests of scientists and experts. Hyun et al. propose that any rule must uphold the two chief goals of “supporting research” and “accommodating diverse moral concerns.” Do support and accommodate suggest the same level of consideration? Similarly, authors of the ISSCR guidelines have “Integrity of the Research Enterprise” as the first in a list of fundamental ethical principles intended to frame guideline development and implementation. They further state that the “primary goals of stem cell research are to advance scientific understanding and to generate evidence for addressing unmet medical and public health needs.”

 

Value Expert Knowledge over Lay Knowledge

 

 

Emphasis on the goals of the research enterprise, combined with common conceptions  of the public as anti-science or too poorly educated to make adequate decisions, encourage the use of engagement models that are more about public indoctrination than public empowerment. Both Hyun, et al., and the ISSCR guidelines, emphasize the need for researchers to communicate with and “engage the public about what they are doing and why it matters.” From their perspective, examples of good engagement practices include the International Summit on Gene Editing, which FitzGerald, Wu, and Bouchard have described as problematic, and public comment periods, which have also proved problematic in cases such as the Notice of Proposed Rulemaking (NPRM) for Revisions to the Common Rule.

Hyun et al. and many others in the scientific community advocate for what is known as the “attitudinal deficit” model – essentially a reframing of the widely criticized “information deficit” model that has been used historically in encounters between science communities and the public. A deficit model is characterized as a one-way conversation with the aim of fostering public support for science. When first introduced, the initial focus was on increasing public knowledge of scientific, technical information, but has in more recent years turned to increasing public knowledge of the potential benefits of science to society. Laudably, the ISSCR guidelines attempt to address some of the potential pitfalls of such an approach (namely ‘science hype’), calling for researchers to “promote accurate, balanced, and responsive public representations of stem cell research.” However, the ISSCR guidelines still fail to move away from the deficit model, advocating for increased transparency and information resources intended to inform rather than engage the public about stem cell research.

Use of the deficit model makes the following assumptions: that the public is at a “deficit” and needs to be informed (of technical information and/or of potential benefits to society); that a reduced deficit will increase support for science and lead to better policy-making; and, that the advancements of science are for the common good. Public engagement events designed using this unidirectional model are often without space for public deliberation or leverage to effect change. Further, by structuring engagement with the aim of fostering public acceptance of scientific research (or, as Hyun et al. put it, to “prevent a public backlash and the implementation of reactive, more restrictive limits on research),” publics are often presented with options in a take-it-or-leave it fashion. What’s more, the available options are often decided upon by experts behind closed doors (e.g. “Scientists Talk Privately About Creating a Synthetic Genome”, 2016). This leaves little room for questioning or “recalibration” of policies, processes, or institutions – exactly contrary to what Hyun, et al. and other scientists purport to want as an outcome.

Despite such criticisms, discussions and decisions regarding emerging biotechnologies continue to take place amongst experts in private. Endy and Zoloth call for “pluralistic, public, and deliberative discussions,” rightfully pointing out that closed-door discussions, such as the private meeting on synthesizing the human genome, do not allow for broader consideration of important ethical questions, potential alternatives, and unintended consequences. Our recommendations on how to operationalize the numerous calls (see also: “Human Germline Genome Editing Debate”) for improved public engagement in ongoing debates will be the subject of our next blog.

 

ABOUT THE AUTHORS

Profile for blog

 

Sam Wu, BS is a research associate at the Pellegrino Center for Clinical Bioethics at Georgetown University Medical Center.

 

Kevin T. FitzGerald, MDiv, PhD, PhD Associate Professor David Lauler Chair for Catholic Health Care Ethics

 

Kevin T. FitzGerald, SJ, PhD is a research associate professor at the Pellegrino Center for Clinical Bioethics, GUMC.

 

 

 

Emerging Biotechnology in Genomics: An Advancing Field, Still Fraught with Questions

BY KEVIN T. FITZGERALD, SJ, PhD, SAMANTHA (SAM) WU, BS, and Fr. CHARLES BOUCHARD, OP

 

In February 2016, it was reported that the Human Fertilization and Embryology Authority (HFEA) granted limited permission for researchers in the UK to genetically modify human embryos, with the hope of elucidating which genes are necessary for successful embryological development. Although Dr. Kathy Niakan and her team at the Francis Crick Institute are only allowed to use the embryos for 14 days, and may not implant a modified embryo in the womb, this permission crossed a frontier in genetic research. It was the first time human embryonic genetic modification had been authorized. This followed the publication of the controversial paper by Liang, et al. (2015) that detailed the researchers’ attempt to modify genes that cause β-thalassaemia in non-viable human embryos using the gene-editing technique, CRISPR. The paper, published in April 2015, kicked off a heated ethical debate.

Now, Frederik Lanner at the Karolinska Institute in Sweden, who got the go-ahead on a project that will also involve gene editing in human embryos, is making preparations to begin those experiments. Earlier this month, it was also reported that another team in China, led by Yong Fan, attempted to use CRISPR to generate HIV-resistant human embryos via the introduction of precise genetic modifications. While this project involved non-viable embryos, much like the research conducted by Liang, et al., “the purpose of this study was to evaluate the technology and establish principles for the introduction of precise genetic modifications in early human embryos.” The ethics committee of Guangzhou Medical University in China approved Fan’s work, and has reported that it has since approved two more similar projects.

The rapid rate of investment of both time and money in new projects involving gene editing and CRISPR makes it clear why the novel gene-editing technique was named Science’s “2015 Breakthrough of the Year.” Indeed, the technique and the research it facilitates have the potential to lead not only to treatments, but also to the elimination of some genetic mutations from the human genome altogether. Other novel biotechnologies, such as next-generation sequencing (NGS), have contributed to the revolution in gene-editing, making sequencing of the genome faster and cheaper than ever before. Clearly, these new technologies are altering, and will alter, medicine in ways that were science fiction only a few years ago.

Scientists have hailed the advancement of these projects with enthusiasm, convinced that the recent approval of the human embryo gene-editing research by funding agencies and IRBs is indicative of wider societal approval. Lanner, for instance, is hopeful that his work will be received with more optimism and less heated debate than the paper by Liang, et al. published just a year ago. At the same time, it is worth nothing that many of the ethical and practical questions, which made and continue to make the genome-editing debate controversial, remain unanswered:

Who should guide the potential impacts of these developments in clinical practice and in broader society?  What applications are ethically permissible?  Who will own these new technologies and the information resultant from their use? How should we regulate and oversee the technology in a way that such advances in science are not prioritized at the expense of public health or to the disadvantage of the poor or marginalized? 

We argue that experts in research, medicine, industry, and policy currently dominate and guide the conversation about R&D and regulation of gene-editing technology – leaving it up to the “experts” to answer the aforementioned questions of ethical and practical importance. But one might also ask, do the “experts” have the appropriate knowledge to know what is in the public’s best interest? What is the “appropriate” or relevant knowledge to make such a judgment? Are we moving forward with these projects because we have answered those questions?

CRISPR, NGS, and many other biotechnologies are all pieces of the broader discussion regarding what the future of science, medicine, and society will look like.  The outcomes of such a discussion may affect our conceptualizations of “disease” and what it means to be a “normal” human being – things that impact every human in society, not just a gathering of experts from a particular social stratum. By restricting the debate to only the “experts” or those who have a vested interest in the technology, society risks maintaining the status quo, or worse, exacerbating existing socioeconomic and health inequalities that disproportionately affect marginalized communities.

 

gene editing

 

Recent Attempts at “Public Engagement”

Many scientists and policymakers have recognized that we are at a pivotal moment in research and health care.  They acknowledge the benefits of collaboration and communication in the effort to achieve improved health.  The FDA, for instance, launched precisionFDA, an online portal that enables “scientists from industry, academia, government and other partners to come together to foster innovation and develop the science behind…[NGS].”

With CRISPR, the international research community was prompted by growing ethical concerns to host the International Summit on Human Gene Editing in Washington, DC in December 2015.  The summit brought together experts from across disciplines and continents charged with the task of discussing the “scientific, ethical, and governance issues” central to the debate on human gene-editing research. That the scientific community organized the conference suggests that it recognizes the need to incorporate a variety of perspectives in the debate. But, recognition alone is insufficient to ensure that such diverse interests are represented in the resulting policy recommendations.

At the conclusion of the summit, Chair of the Organizing Committee, David Baltimore, proposed guidelines for regulating human gene-editing research. The guidelines, however, were crafted to reflect the perspectives of scientists and academics, along with a few members of the general public who were invited and present. The guidelines lacked input from other public groups for whom human genome editing could have many implications. Unfortunately, the inadequate model of “public engagement” employed at the Summit is actually quite common across science policy issues.

Dr. Ruha Benjamin, Princeton University professor and author of People’s Science: Bodies & Rights on the Stem Cell Frontier, notes that the processes currently used to gauge public opinion on new scientific developments often create only an “illusion of opening up the science.” Institutions acknowledge, to some degree, the importance of gauging public interests and goals when it comes to scientific progress. The list of terms and mechanisms used in an attempt to determine such interests and goals is long: “public conferences,” “public meeting,” “public comment period, “public forum,” “public engagement,” and so on. Closer inspection of these mechanisms and their outcomes reveal several issues with the scientific community’s current “public engagement” efforts: 1) there is a lack of evidence and consensus to suggest which mechanism is most appropriate and when, 2) the public’s diversity of values and goals are underrepresented by a handful of public representatives, often selected by the host organization themselves, 3) differences are often resolved with more “expert” or “technical” information, rather than deeper discussion of differences in values or goals (expert knowledge is prioritized over lay knowledge), 4) the mechanism’s design provides the public with insufficient leverage to effect change in research or policy development, and 5) more often than not, there are insufficient evaluation measures in place to reinforce accountability. While these mechanisms have the potential to inform and engage the public in policy discussions that bear directly on the common good, these obstacles often lead them to fall short and leave voices unheard.

Our ethical tradition of fostering the common good says we need broader discussions that go beyond the one-way discussion that focuses on informing the public to foster “public acceptance” — beyond this “illusion of opening up the science.” We need deliberative, two-way discussions that make values and goals explicit, and that actively involve the public as community members and participants in research, clinical practice and decision-making. With genome editing, it is imperative that these discussions happen now before boundaries are crossed, even inadvertently, that cause harm to many people which cannot be readily remedied.

Moving forward, we suggest that academic institutions – increasingly home to interdisciplinary efforts and collaborations – make a much greater effort to research and design processes that engage public stakeholders in the discussion around genome editing and, more broadly, emerging biotechnologies. Several organizations have already implemented biomedical research tools and platforms created with participant preferences, values, and communities in mind that can serve as a good starting point. We also call for greater collaboration between natural science and social science researchers, which will increase our understanding of the assumptions and factors that influence policy-making and inform the design of mechanisms intended to generate a more open, deliberative public dialogue.

Sustained public engagement is essential to ensuring that science and medicine’s advancements continue to address broad public needs, and not only those of the few. Indeed, there have been calls for greater public involvement in the genome-editing debate. Despite these calls, however, the field continues to proceed with controversial experiments while ethical and practical questions remain unanswered, with scientists presuming that IRB approval of their controversial projects means that the public is becoming more accepting with “the passage of time.” It is, thus, time to increase our efforts to “open up” the science, not just to the experts, but also to those whose lives will be impacted and whose voices have yet to be heard.

 

ABOUT THE AUTHORS

Fr. Kevin FitzGerald, S.J., is research associate professor and Samantha (Sam) Wu, B.S., is a research associate at the Pellegrino Center for Clinical Bioethics at Georgetown University Medical Center; Fr. Charles Bouchard, O.P., is Senior Director, Theology and Ethics, at the Catholic Health Association of the United States.