The need to set explicit goals for human germline gene editing public dialogues.

Given the potentially large ethical and societal implications of human germline gene editing (HGGE) the urgent need for public and stakeholder engagement (PSE) has been repeatedly expressed. However, the explicit goals of such PSE efforts often remain poorly defined. In this program report, we outline the goals of our Dutch project called De DNA dialogen (The DNA dialogues). We believe that setting explicit goals in advance is essential to enable meaningful PSE efforts. Moreover, it enables the evaluation of our engagement efforts. The following four goals, which result from intensive consultations among the transdisciplinary projects' consortium members and based on the literature, form the foundation for how we will engage the public and stakeholders in deliberation about HGGE: 1) Enable publics and stakeholders to deliberate on "what if" questions, before considering "whether" and "how" questions regarding HGGE, 2) Investigate agreement and disagreement in values and beliefs regarding HGGE in order to agree and disagree more precisely, 3) Involve diverse publics with various perspectives, with a focus on those that are typically underrepresented in PSE, 4) Enable societally aligned policy making by providing policymakers, health care professionals and legal experts insight into how values are weighed and ascribed meaning in the context of HGGE by various publics, and how these values relate to the principles of democratic rule of law and fundamental rights. The effort to describe our goals in detail may serve as an example and can inform future initiatives striving for open science and open governance in the context of PSE.

"What if" should precede "whether" and "how" in the social conversation around human germline gene editing.

Given the potential large ethical and societal implications of human germline gene editing (HGGE) the urgent need for public and stakeholder engagement (PSE) has been repeatedly expressed. In this short communication, we aim to provide directions for broad and inclusive PSE by emphasizing the importance of futures literacy, which is a skill to imagine diverse and multiple futures and to use these as lenses to look at the present anew. By first addressing "what if" questions in PSE, different futures come into focus and limitations that arise when starting with the "whether" or "how" questions about HGGE can be avoided. Futures literacy can also aid in the goal of societal alignment, as "what if" questions can be answered in many different ways, thereby opening up the conversation to explore a multitude of values and needs of various publics. Broad and inclusive PSE on HGGE starts with asking the right questions.

Eight tips for using art and design to start dialogue about science.

To share our lessons learned from using art and design to start public dialogue concerning genomics, we co-created a course called 'Art & Genomics', together with designers Bertrand Burgers and Mirte de Wit. Here, we aim to share our tips for any scientist who wants to harness creative design to trigger public engagement, illustrated by student experiences as well as our own.

Changes in opinions about human germline gene editing as a result of the Dutch DNA-dialogue project.

Public engagement for Human Germline Genome Editing (HGGE) has often been called for, for example by the WHO. However, the impact of public engagement remains largely unknown. This study reports on public engagement outcomes in the context of a public dialogue project about HGGE in the Netherlands; the DNA-dialogue. The aim was to inquire opinions and opinion change regarding HGGE. A questionnaire was distributed on a national level (n = 2381) and a dialogue level (n = 414). The results indicate that the majority of the Dutch population agrees with the use of HGGE to prevent severe genetic diseases (68.6%), unlike the use to protect against infectious diseases (39.7%), or for enhancement (8.5%). No indications of change in these acceptance rates as a result of dialogue participation were found. The results did provide a tentative indication that participation in dialogue may lead to less negative opinions about HGGE (χ2(1) = 5.14, p = 0.023, OR = 0.56, 95% CI [0.34, 0.93]). While it was not a goal of the project to make people more accepting towards HGGE, this might be the effect of exposure to opinions that are less often heard in the global debate. We conclude that dialogue may lead to different outcomes for different people, depending on their characteristics and their entrance attitude, but does not appear to systematically direct people towards a certain opinion. The self-reported, impacts of dialogue participation included no impact, strengthening of opinion, enabling of forming a first opinion, more insight into the potential implications of HGGE, and a better understanding of other people's perspectives.

The DNA-Dialogue: A Broad Societal Dialogue About Human Germline Genome Editing in the Netherlands.

For years, calls for public involvement in the debate concerning the acceptability of human germline genome editing (HGGE) have been made. A multidisciplinary consortium of 11 organizations in the Netherlands organized a broad societal dialogue to inquire about the views of Dutch society toward HGGE. The project aimed to reach a wide and diverse audience and to stimulate a collective process of deliberative opinion forming and reflection. To that end, several instruments and formats were developed and employed. We present the results of 27 moderated dialogues organized between October 2019 and October 2020. Overall, participants of the dialogues were capable of assessing and discussing the subject of HGGE in a nuanced way. Analysis of these dialogues shows that in general, participants had no fundamental and absolute objections toward HGGE technology. However, they only deemed HGGE to be acceptable when it is used to prevent serious heritable diseases and under strict conditions, without affecting important (societal) values. There was a small group of participants who found HGGE fundamentally unacceptable because it would cross natural, socio-ethical, or religious boundaries.

Experts in science communication: A shift from neutral encyclopedia to equal participant in dialogue.

Even if the predominant model of science communication with the public is now based on dialogue, many experts still adhere to the outdated deficit model of informing the public.

In the Era of the Actionable Genome, Everyone is Responsible.

Genomics professionals and the general public have a responsibility to bridge the gap between science and society. The general public has a responsibility to deliberate, as their choices not only impact themselves but also shape society. Conversely, genomics professionals have a responsibility to enable the process of opinion formation.

Dose-effect of maternal serotonin reuptake inhibitor use during pregnancy on birth outcomes: A prospective cohort study.

BACKGROUND: While antidepressant use during pregnancy is increasingly common, there is concern about the possible effects of in-utero antidepressant exposure on the child. Our objective was to examine whether there is a dose-effect of maternal serotonin reuptake inhibitors (SRI) during pregnancy on birth outcomes. METHODS: Women between 12 and 16 weeks of gestation, who were using an SRI, were eligible for participation in this nation-wide prospective observational cohort study. Recruitment took place between April 2015 and February 2018 (n = 145). SRI exposure and psychopathology symptoms were assessed throughout pregnancy. Exposure was defined as SRI standardized dose at 36 weeks of gestation and mean SRI standardized dose over total pregnancy. Multivariable linear and logistic regression were used to examine the associations with birth weight, gestational age at birth, and being small for gestational age. RESULTS: Maternal SRI dose at 36 weeks of gestation was significantly associated with birth weight (adjusted ß = -180.7, 95%CI -301.1;-60.2, p-value < 0.01) as was mean SRI standardized dose during total pregnancy (adjusted ß = -187.3, 95%CI -322.0;-52.6, p-value < 0.01). No significant associations between maternal SRI dose and gestational age or being small for gestational age were observed. LIMITATIONS: Although prospective, we cannot make full causal inferences given that we did not randomize women to different dosages. CONCLUSION: These findings suggest that careful dosing of SRI use during pregnancy may prevent a negative impact on birth weight and indicate the need for further investigation of causality.

Offering a choice between NIPT and invasive PND in prenatal genetic counseling: the impact of clinician characteristics on patients' test uptake.

Testing options for pregnant women at increased risk of common aneuploidies are non-invasive prenatal testing (NIPT) and invasive prenatal diagnosis (PND). Clinicians are challenged to comprehensively discuss the complex information in a patient-centered and non-directive manner, to allow for patients' informed decision-making. This study explored the information-centeredness, patient-centeredness, and level of non-directivity of different clinicians and examined group differences between their patients. First, semi-structured interviews with four senior obstetricians and one senior nurse were held regarding their information provision, their adaptation of a patient-centered attitude, and their practice of non-directivity. Interviews were transcribed verbatim and rated by four independent researchers. Secondly, 181 pregnant women were included in the study, of whom 82% opted for NIPT and 18% chose PND. Between clinicians, we assessed the distribution of choice ratios, patients' impression of clinicians' test preferences, and patients' knowledge scores. The results indicate that clinicians do not differ in their information-centeredness, but do differ in their patient-centeredness and their level of non-directivity. Significant differences in patients' NIPT/PND ratios were observed between clinicians, with the largest difference being 35 vs. 4% opting for invasive PND. Between 9 and 22% of the patients had an impression of their clinician's preference and chose in accordance with this preference. Patients' overall knowledge scores did not differ across clinicians. In conclusion, the differences in NIPT/PND ratios between clinicians indicate that clinicians' differing counseling approaches affect the choices their patients make. The interviews indicate a possible framing effect which may unintentionally steer the decision-making process.