Ethical and Social insights into Synthetic Biology: Bibliometric approach and predicting research fronts in POST-COVID-19 era

doi:10.21203/rs.3.rs-1215578/v1

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Ethical and Social insights into Synthetic Biology: Bibliometric approach and predicting research fronts in POST-COVID-19 era

https://doi.org/10.21203/rs.3.rs-1215578/v1

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As a revolutionary biological science and technology, synthetic biology (SynBio) has already spread its influence from natural science to philosophy and social sciences by introducing biosafety, biosecurity, environmental and ethical issues to society. The current study aims to elaborate the intellectual bases and research front of the synthetic biology field in the sphere of humanities and social sciences with knowledge mapping and bibliometric methods. The literature records from the Social Sciences Citation Index (SSCI) and Arts & Humanities Citation Index (A&HCI) in the Web of Science Core Collection from 1982 to 2021 were collected and analyzed to illustrate the intellectual structure of humanities and social researches of SynBio. This study profiled the hotspots of research focus on its governance, philosophical and ethical concerns, and relevant technologies. This study offers clues and enlightenment for the stakeholders and researchers to follow the progress of this emerging discipline and technology and to understand the cutting-edge ideas and future form of this field, which takes on greater significance in the post-COVID-19 era.

synthetic biology

social sciences

bioethical concerns

playing god

biosecurity

biosafety

Synthetic Biology related literature in Social sphere examined systematically.
History and Philosophy of Science observed as dominating research front.
In post-COVID-19 era, bioterrorism, biosecurity and politicians are serious concern.

Life sciences experienced three major revolutions since 20th century, from the cellular and molecular biology in 1960s, genomics and systematic biology after 2000 to the convergence biological science, which was represented by SynBio. It has evolved over a huge spectrum of interdisciplinary continuum which includes life science branches such as biochemistry, microbiology, molecular biology, systematic biology, and non-life science branches like computer sciences and engineering sciences. Consequently, there is no wildly accepted definition of SynBio yet. For the scientists in bioengineering field, SynBio is defined as “the engineering-driven building of increasingly complex biological entities for novel applications” [1]. Luis Serrano (2007) put forward that a group of European experts defined SynBio together as “the engineering of biology: the synthesis of complex, biologically based (or inspired) systems, which display functions that do not exist in nature”, and distinguished SynBio from Systems Biology by ‘engineering’ and ‘synthesis of novel functions’. Meanwhile, in David Gilbert (2010)’s definition, the top-bottom and bottom-top approaches of SynBio research were emphasized. In current research, we agreed that SynBio can be defined as “the design and construction of novel biological parts, devices and systems, as well as the redesign of existing natural biological systems, for useful purposes” (Roberts et al. 2013), and Gómez-Tatay and Hernández-Andreu (2019) also stressed several features of SynBio including “aims to the creation of something fundamentally new, biological parts or systems not otherwise found in nature”. This definition distinguishes SynBio from other biological disciplines clearly by the novelty of productions which brings about uncertainty in ethical issues and biosafety and biosecurity concerns, so as to catch the attention of sociologists, ethicists and stakeholders.

The world has witnessed many breakthroughs in many fields, such as biomedicine and energy industry with SynBio’s support [2, 3]. The heterologous production of precursors to artemisinin— a widely used antimalarial drug was realized with engineered yeast in 2006, demonstrating enormous potential of SynBio in Biomedicine (Ro et al. 2006). SynBio are used to design DNA-based information storage and communication and processing systems for genetic coding[4, 5]. In industry, engineered microbial cells were used for biofuel production [6]. Generally, SynBio works as a game-changer for its tremendous potentials.

However, despite all the benefits it brings to human beings, SynBio also comes with risks and concerns as a dual-use research. SynBio’s products are non-natural artificial life with endogenous uncertainty. Before its emergence, human beings have no experience or knowledge of its existence and nature, and this product itself may have the possibility of self-reproduction and genetic evolution, which could magnify the uncertainty dramatically. This uncertainty itself implies biosafety and biosecurity risks that could cause harm to human beings, organisms or living environment, and leads to psychological and cognitive risks at the individual and social levels, as well as other significant impacts on human society. Therefore, SynBio has also become the research object in humanities and social sciences, attracting wide attention from researchers and stakeholders in philosophy and ethics, policy and laws, science communication and public understanding, and intellectual property. As ethical concerns, SynBio arouse us to think about the intrinsic value of life (Link 2013), the dignity of life, integrity of nature, and the relationship between God and his creation (Heavy 2013). Meanwhile, the novelty of SynBio undermined the feasibility of previous policies or laws for biological or bioengineering practices, and appealing to new governance methods and ethical regulations. Some researchers concerned about SynBio from the public opinion view, and tested the relationship more information and deliberation and public support (Kronberger et al. 2012). Besides, the intellectual property and commercialization of SynBio have also become important research areas and issues for sociologists [7]. All these demonstrate that SynBio has impacted greatly on the humanities and social sciences researches, and would further spread to human society globally.

Meanwhile, in the context of the great influence of global pandemics such as COVID-19, HINI, SARS and MERS on people [8], the public's concern about the development of novel biotechnology will be magnified significantly. Thus, in the post-COVID-19 era, SynBio, the revolutionary discipline and technology, can encounter new possible risks and obstacles in the development, which consequently hinders the world from the possible solutions and benefits that SynBio might offer and leaves less hope for human beings. It is time to reconsider the sociological and philosophical barriers to the development of SynBio, in order to provide more opportunities for SynBio to benefit and help people.

Therefore, it is necessary to systematically review and summarize the researches in humanities and social sciences of SynBio, and elaborate the intellectual bases (the knowledge origin of current collected literatures, usually exists as references) and research fronts (the dominant research themes of collected literatures, can be extracted from the keywords and titles of the literatures) of this field, so as to provide some reference for the future research on the public understanding, ethics and governance of SynBio. Some studies have attempted to review the natural science progress of SynBio, or argued on partial aspects of its social sciences so far. For instance, Shapira ⁽²⁰¹⁷⁾ reviewed the SynBio researches in the sphere of natural sciences and gave the practical definition and conceptual boundary of SynBio in the study, which helped a lot for collecting the regarding literatures. Hayry ⁽²⁰¹⁷⁾ elaborated the ethical concerns related to SynBio and its relatedness to Genetically Modified Organisms (GMO). Similarly, Patrick Heavey ⁽²⁰¹⁷⁾ underlined the moral perspective, integrity of nature, and essence of spirituality [12].

However, there is few research that has hitherto reviewed the entire pool of social sciences literatures of SynBio, instead of the natural sciences ones. In consideration of the huge amounts of research articles for review, traditional review are either unable to avoid bias, subjectivity and incompleteness, or time-consuming and lack of the diversity of analysis methods [13]. Therefore, in current research we introduce bibliometric methods, co-word analysis, co-citation analysis and some other algorithms to analyze the literatures systematically and holistically, and utilize knowledge mapping and visualization technology to provide intuitive and comprehensible insights and conclusions. Specifically, a set of favorable bibliometric software such as Citespace and VOSviewer are used for analyzing.

Above all, the current study aims to solve the following questions:

Research Question 1 (RQ1): Generally, how does the literatures distribution look like? It’s about to illustrate the yearly growth status, the distribution of literatures on country and institution level, and the dominant research areas of all regarding literatures.

RQ2: What is the intellectual bases of this area?

RQ3: What are the research hotspots in this research area?

RQ4: What are the potential research trends of SynBio social science studies?

2.1. Bibliometrics, Co-occurrence Analysis and Visualization

In current research, bibliometrics and co-occurrence analysis methods were used to illustrate and explicit the evolution path and knowledge structure of SynBio literatures in social sphere.

Bibliometric approaches, referring to the measurement of text and information, help to understand the pattern of literatures growth, highlight the remarkable research categories, productive research units such as researchers, institutions and countries and the impactful literatures and references. Instead of the partial understanding of certain area from individual views, bibliometric methods give a bigger and neutral image of the general whole area, specifically the pool of literatures herein, and was later upgraded by Moss's Database Information Visualization and Analysis system (DIVA) [14] which combines bibliometrics data with visualization techniques to assist researchers understand scientific literatures systematically and visually. Moreover, co-occurrence analysis, including co-word analysis, co-citation analysis and collaboration analysis, works as powerful and mature methods for detecting knowledge structure in recent years.

Co-word analysis of keywords is to generate the networks of keywords based on their co-occurrence relationship in the same literatures, which implies their similarity and relevance at the level of meaning, and helps to explore the thematic evolution, research fronts and trends of a given research field (Cobo et al. 2011). Co-citation analysis has been proved as a well-known approach for intellectual structure detecting [15], functions better when the co-citation networks are well clustered (Chen et al. 2010), and can be used to predict the future / emerging trends (Van Eck et al. 2010). Given that SynBio is highly interdisciplinary and dominated by highly specialized research themes, it can be much convenient to find out research gaps among its divergent intellectual knowledge bases with co-citation approach. In recent years, visualization techniques are utilized in co-occurrence analysis, the target units in co-occurrence networks such as cited references, keywords exist as nodes, the co-occurrence relationship between the units is exhibited as edges which connected the nodes, then all the target units can be shown together in an informative visual network.

Several tools and software have been developed to analyze and visualize the bibliometric data in the last few years, such as CiteSpace and VOSviewer. Cite-space is a Java software designed for analyzing and visualizing co-occurrence data [17], especially good at co-citation analysis, which facilitate the analysis of emerging trends and transient patterns in scientific literatures (Chen 2006). VOSviewer was developed for creating, visualizing, and exploring bibliometric maps of science, and good at text mining and visualization (Van Eck et al. 2011). This study uses VOSviewer and CiteSpace, two mature visualization tools with respective advantages, to analyze the SynBio literatures in the sphere of social sciences.

2.2. Data collection

This study focuses on the humanities and social sciences original and impactful researches of SynBio, so we collected the article and review records from Web of Science Core Collection, including SSCI and A&HCI, as data source. To eliminate the risk of skewness from collecting records, the conference proceedings, letters, retracted manuscripts, book chapters were excluded.

Owing to its rich connotation and without well accepted definition of SynBio, the relevant terms for retrieving need to be organized systematically. To confront the challenges from dealing with interdisciplinary definitions [18], many scholars adopted expert-defined keyword methods, such as [19, 20], or other semi-automatic retrieving methods. To cope with the validity and reliability related challenges, we cited the concept system of SynBio from Shapira ⁽²⁰¹⁷⁾, and upgraded and created a novel definition system of SynBio according to the relevant elements or definitions of SynBio in social science context. For instance, we removed the terms which actually refers to cell phones instead of artificial cells for disambiguation, and added more terms about SynBio like “protocell” and “DiyBio”. Eventually, 428 article records and 2474 references were collected on April 24th, 2021. The process of creating the definition system of SynBio was listed in Table 1.

Table 1

Search strategy
Steps	Operations	Results
1	Search in SSCI and A&HCI based on the search strategy offered by Shapira (2017) and check the search results	Found many irrelevant records due to the improper searching terms such as "artificial * cell phone"
2	Search the terms about SynBio provided by Shapira one by one in SSCI and A&HCI and check the results; remove the terms with irrelevant records and maintain the effective ones	“Synthetic biolog ” “synthetic dna” “synthetic genom ” “synthetic gene”
3	Add relevant terms from the retrieved literatures and other experts' definitions of SynBio and test the terms in turn	New keywords: "synthetic cell" "artificial cell" "Do-it- yourself biology " "DIYbio" "DIY biology " "biobrick" "protocell virus" "protocell"
4	Formula the search strategy with the terms above and Boolean operators, as well as remove the irrelevant ones with Boolean operator “NOT” Combine the keywords obtained by the two methods and conduct the fourth screening to obtain the final search formula	The final search strategy as follows: TS=(“synthetic biolog” OR “synthetic dna” OR “synthetic genom” OR “synthetic gene” OR “synthetic cell” OR “artificial cell” OR “Do-it-yourself biology” OR “DIYbio” OR “DIY biology” OR biobrick) OR (TS= (“artificial life” OR “artificial lives”) AND TS=(protocell OR virus)) OR (TS=(protocell) NOT TS=(“dichroic reflector” OR architecture))

3.1. RQ1: Literatures Distribution

The quantity of literatures grew in succession from 2006 to 2020 generally, and the peak appears on 2020, so there might be more researches on going. Figure 1 illustrated the yearly growth of publication records. The earliest record in this collection is “Social Responsibility in an Age of Synthetic Biology” by Sheldon Krimsky (1982), it highlighted the risk of rDNA as bioweapon and appealed to harness rDNA technology and the social responsibility of SynBio research to society far early then the emergence of the first artificial cell “Synthia”, which represented the early concerns on SynBio.

3.1.1. Most productive countries and institutions

The list of top productive countries is dominated by the developed countries (Table 2). Specifically, two English speaking countries, i.e. US and UK, take the top 2 position and account for over 50% of the total publications, which are followed by Germany, Netherlands, France and other European countries. This is in line with policies and advances of SynBio research in the United States and Europe, such as New Directions: The Ethics of Synthetic Biology and Emerging Technologies released in 2010 by Presidential Commission for the Study of Bioethical Issues in USA, Final Opinion on Synthetic Biology III: Risks to the environment and biodiversity related to synthetic biology and research priorities in the field of synthetic biology released in 2015 by European Commission- Scientific Committees.

Table 2

Publication records of top prolific countries or regions
Rank	Country/Region	Publications	Proportion (%)
1	USA	126	29.439
2	England	83	19.393
3	Germany	36	8.411
4	Netherlands	33	7.71
5	France	30	7.009
6	Spain	30	7.009
7	Scotland	27	6.308
8	Switzerland	24	5.607
9	Austria	20	4.673
10	Canada	18	4.206

The most prolific institutes include the Universities of Edinburgh (25 records), University of Manchester (18), Georgia Institute of Technology (10), University of Copenhagen (9) and University of Zurich (9). The British universities distinguished from all the contributors. Owing to Professor Shapira of the University of Manchester is also affiliated in Georgia Institute of Technology, these two institutions share the publication records.

In order to understand the collaboration among institutions, VOSviewer was used to illustrate their co-occurrence networks here (Fig. 2). We use Density Visualization function in VOSviewer to mark the most productive institutions and their collaborations, in which two major clusters are generated in red and green color. There are two research teams in UK that are closely internal connected in their network, leading by University of Edinburgh, with University of Lancaster, University of Exeter, and leading by University of Manchester, with University of Sheffield, University of Oxford. Moreover, in the red cluster, several universities from USA are alse well connected, including Massachusetts Institute of Technology, University of California at Los Angeles, University of Pennsylvania and Harvard University. Institutions from continental Europe have also formed networks in green cluster, including University of Helsinki, University of Vienna, University of Zurich and some other institutions, as shown in Fig. 2.

With the same approach, we illustrated the collaborative network of researchers in this field (Fig. 3), three teams standout, including Calvert’s team in University of Edinburgh, Shapira's team in University of Manchester, Knuuttila’s team in University of Vienna, as shown in Fig. 3.

3.1.2. Research areas

In this field, the research area with the most publications is history and philosophy of science (Table 3), followed by ethics, social sciences biomedical and philosophy. Obviously, the philosophical and ethical issues serve as the dominant theme of this field, and account for 44.5% of the publication records. Beside the ethics, philosophy and social sciences domains, environmental studies and communication emerge as novel perspectives to explore the social impact of SynBio.

Table 3

Top 10 Research areas of SynBio related social science literatures
Rank	Research areas	Number of Publications
1	history and philosophy of science	124	28.972
2	ethics	91	21.262
3	social sciences biomedical	55	12.85
4	philosophy	51	11.916
5	social issues	43	10.047
6	multidisciplinary sciences	34	7.944
7	environmental studies	29	6.776
8	medical ethics	27	6.308
9	engineering multidisciplinary	24	5.607
10	communication	22	5.14

3.2. RQ2: Intellectual bases of current field

Research fronts and intellectual bases are fundamental concepts in information science, the former focus on the grouping of concepts and underlying research issues, while the latter refer to the citation and co-citation footprint in scientific literature (Chen, 2006), which helps to detect the evolvement and knowledge origin of certain research fields. In this section, we used Citespace software to analyze the references of the collected records, especially the co-citation relationship of these references and of its source titles respectively.

We found the top highly co-cited references, which are visualized as nodes by the software in the co-cited reference network, and the co-citation relationship of each pair of references is visualized as the edge between the nodes. Then we conducted a cluster analysis of the co-cited references and labeled the clusters with the embedded algorism Log-Likelihood Ratio to elaborate the themes of the clustered references within the network. The highly co-cited journals are listed at the end of this section to facilitate the analysis of the intellectual bases.

Citespace software has several advantages when dealing with co-citation data. First, it can detect highly co-cited references (Table 4), the nodes with high co-citation frequency in the network. Meanwhile, the nodes in the network can also be clustered according to their spatial distance, so the nodes with details can be classified and labeled as clusters to extract knowledge from detailed information by Citespace's built-in text mining algorithms, such as the Log-Like Ratio whose effectiveness was introduced by Chen (2010).

Table 4

Top 10 highly co-cited references
Frequency	Title	Author	Year	DOI
46	Creation of a bacterial cell controlled by a chemically synthesized genome	Daniel G. Gibson, et al	2010	10.1126/science.1190719
32	Knowledge-making distinctions in synthetic biology	Maureen A. O'Malley, et al	2008	10.1002/bies.20664
26	Foundations for engineering biology	Drew Endy	2005	10.1038/nature04342
25	Developing a framework for responsible innovation	Jack Stilgoe, et al	2013	10.1016/j.respol.2013.05.008
19	Synthetic biology and the ethics of knowledge	Thomas Douglas & Julian Savulescu	2010	10.1136/jme.2010.038232
18	That was the synthetic biology that was	Luis Campos	2009	10.1007/978-90-481-2678-1_2
17	Tales of emergence: Synthetic biology as a scientific community in the making	Susan Molyneux-Hodgson & Morgan Meyer	2009	10.1017/S1745855209990019
16	Five hard truths for synthetic biology	Roberta Kwok	2010	10.1038/463288a
16	Responsible research and innovation: from science in society to science for society, with society	Richard Owen, et al	2012	10.1093/scipol/scs093
15	Commentary diffusion of synthetic biology: A challenge to biosafety	Markus Schmidt, et al	2008	10.1007/s11693-009-9034-7

3.2.1. Highly co-cited references related to SynBio in social sciences

We listed the top 10 references with the high frequency of co-citation (Table 4) and other details of the author, publishing year and DOIs. The natural science results worked as the knowledge source at the early stage. Then the social science researches took the central place and enriched the studies in this field with its theories. Among them, Owen (2012) provided a historical overview of the concept and three features of responsible innovation (RI) after the Horizon 2020 Strategy was put forward by EU. While Stilgoe (2013) systematically constructed a framework to integrate SynBio and RI, illuminated four integrated dimensions of RI in SynBio research, including anticipation, reflexivity, inclusion and responsiveness, and discussed the universality of RI in SynBio beyond the use in UK Research Councils and the scientific communities. Douglas and Savulescu (2010) introduced ethics of knowledge into the research on SynBio based on the “misuse of knowledge”, initiated a new research domain and provoked widespread debate.

3.2.2. Intellectual bases: Cluster analysis of co-cited references

All the co-cited references in the network are clustered, labeled and visualized with Citespace, the distribution of each cluster is shown in Fig. 4. The clusters are identified by its size (Cluster #0 has most nodes) and ranked by their mean year (Table 5). The silhouette value indexed the similarity of nodes in the same cluster, and each of them is over 0.7, which indicates the homogeneity of the nodes within the same cluster for analysis. The clusters can be divided into 3 stages generally, i.e. the “knowledge transfer” stage (Cluster #0, #1 and #12), the “public engagement” stage (Cluster #2, #4, #5 and #11) and the “diversified reflection” stage (Cluster #3, #6, #8, #10 and #9).

Table 5

Size, silhouette and labels of each cluster in co-cited reference network
Cluster ID	Size	Silhouette	mean(Year)	Label (LLR)
0	97	0.852	2007	making big promises
1	57	0.746	2011	public attitude
12	10	0.959	2012	genome editing
2	43	0.831	2013	public perception
4	41	0.949	2013	diy biology
5	35	0.725	2013	participating mean
11	13	0.973	2013	living machine
3	43	0.916	2014	regenesis life
6	34	0.944	2014	social science
8	24	0.951	2015	multi-disciplinary research centre
10	16	0.934	2015	constructive sustainability assessment
9	18	0.962	2016	synthetic biology application

The knowledge transfer stage is the earliest one and contains 3 clusters, including the biggest two clusters (#0 & #1), well connected and located on the right part of Fig. 4. In this stage, the concepts and distinctions from relative disciplines [21], relative technologies and potential applications of SynBio were widely introduced into humanities and social sciences, as well as philosophical studies, during which SynBio served as a novel issue, people crave for its bright prospect, commercial value, intellectual property (Calvert, 2008) and technology potentials. Besides, some researches focus on the ethical issues about SynBio as well.

In the public engagement stage, public perception and public participation became the major concern in this field. No matter the experiments and practices of public on biological materials with SynBio technology, like Do-it-yourself (DIY) biology, or the perception, governance, monitoring, policy making about SynBio, public engagement appears as the nonnegligible and inevitable issue since the emergence of SynBio itself. The clusters about public participation connected closely in this stage, while the Cluster #11 living machine, locating separately from them in the same period, indicates the concerns on the ethical and philosophical discuss about SynBio.

The latest stage “diversified reflection” turned out to be multiple regarding themes, and the researchers reevaluated and reflected on SynBio from divergent perspectives. Besides the previous issues in the last two stages, novel technologies used in SynBio, innovative administration and management, sustainability assessment and other various themes supplied various knowledge bases for this field in latest period. Novel and continuously improving technologies like CRISPR [22] and gene editing are hot topics of controversy in recent years, especially after the “gene-edited babies” event, which aroused people’s attention on biotechnology ethics. These studies reconsidered the general problems emerged in the development of new technologies, such as the lack of transparent regulatory standards, outdated management regulations, and tedious and time-consuming clinical trials, and provide references to avoid similar problems which harass SynBio. The multi-disciplinary research centre (Vermeulen 2018) and its innovative management have also caught much attention in recent years. Specially, "responsible innovation" stands out as one of the promising solutions for the bioethical issues (Vermeulen et al. 2017) of emerging biosciences and biotechnologies, which impacts on the daily practices and behaviors of scientists and the outcomes of their studies (Pansera et al 2020).

3.2.3. Highly co-cited journals

Using the same research method as in 3.2.2, we obtained the top 20 highly co-cited journals table (Table 6), including the journal titles, co-cited frequency of journals, centrality in the network, the mean year of being cited and half-life of each journal. It indicated that the early source titles are mainly from the field of natural sciences, while in the recent years, the journals from the field of social sciences take the dominant position, and there is a shift in the sources of knowledge in this field. Among all the high-centrality nodes which have structural importance, Biosocieties, Bioessays, Social Studies of Science, Public Understanding of Science and Research Policy are the prominent knowledge sources for the development of this field in social science sphere.

Table 6

Top 20 highly co-cited journals of SynBio related social science literature
Frequency	Centrality	Cited Journal	Mean Year	Half-life
258	0.1	Nature	2007	8.5
229	0.05	Science	2007	8.5
149	0.06	Nature Biotechnology	2007	8.5
120	0.07	EMBO Reports	2007	8.5
101	0.1	Proceedings of the National Academy of Sciences	2009	7.5
80	0.24	Biosocieties	2009	5.5
73	0.07	Nature Reviews Genetics	2009	6.5
70	0.08	Molecular Systems Biology	2010	4.5
66	0.11	Bioessays	2009	5.5
66	0.1	Social Studies of Science	2012	4.5
64	0.08	PLOS ONE	2012	5.5
63	0.02	Science Technology & Human Value	2009	7.5
62	0.13	Public Understanding of Science	2012	4.5
59	0.09	Nanoethics	2011	5.5
59	0.03	Science and Engineering Ethics	2012	4.5
57	0.12	Research Policy	2014	3.5
52	0.11	PLOS Biology	2012	3.5
50	0.06	Trends in Biotechnology	2012	6.5
49	0.07	Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences	2012	4.5
43	0.09	Science and Public Policy	2014	3.5

3.3. RQ3: Hotspots in SynBio related literatures in social sciences

In this section, VOSviewer software was utilized to conduct co-word analysis on the keywords of all literatures collected in this field, and to visualize the network of co-word relationship in Fig. 5 with the built-in algorithms. In this science mapping practice, keywords in the collected literatures are linked according to their co-occurrence relationship, in which the keywords with larger font have higher co-occurrence frequency and impact. With the built-in clustering algorithm of the software, four clusters emerged and were marked as red, green, blue and yellow respectively in Fig. 5, each cluster represents a sub-theme of current field.

Cluster 1 (red): this cluster represents the themes mainly about the governance of SynBio, containing three aspects of keywords such as assessment and standards, responsible research and innovation (RRI), and public engagement. In addition to the searched terms like “synthetic biology”, other high impact keywords in this cluster are governance, standards, values, technology assessment; Responsible Research and Innovation; public engagement, science communication, media, diybio and International Genetically Engineered Machine (iGEM). Technology assessment, a set of wildly used methods for assessment and governance on emerging technologies during 1970s to 1990s, aimed to provide early warning by evaluating emerging technologies so that potential and unexpected negative impacts can be corrected and remedied in a timely manner, while it concerned more on risk evaluation rather than ethical issues. After that, Ethics, Legal and Social Issues (ELSI) programme was put forward alongside with the Human Genome Project by National Institute of Health, and focus more on interdisciplinary researches and the interaction between different stakeholders in society, and refer to the ethics and legitimation of the researches (Gregorowius & Deplazes-Zemp 2016). However, ELSI practice enacted the epistemological gap as a division of labor “where scientists do science and leave social, moral and ethical questions to experts – ethicists, theologians, lawyers and social scientists”, and are often based on a simplified linear model of innovation pathways and outcomes (Marris et al. 2015). Then, RI (or RRI) was promoted and supplied an interdisciplinary frame for the governance of SynBio and emphasized the public participation in the whole process of innovation, including the assessment of technology itself, offering the idea of social needs and wishes, and decision on the final plan to meet them. Actually, Gregorowius and Deplazes-Zemp (2016) pointed out that TA and ELSI research can be regarded as the early development stage and predecessor of RRI. So, in this cluster, all three aspects of keywords refer to the responsible governance of SynBio and can be covered in the frame of RRI, as shown in the Fig. 6.

Cluster 2 (yellow): Keywords in this cluster represent the studies mainly related to philosophical issues of synthetic biology, including “moral status”, “playing god”, “artificial life”, “self-organization”, “natural selection” and bioethics. These studies highlighted the philosophical issues of SynBio and its product, i.e. the artificial life. Some religious strong believers oppose to SynBio because the creation of artificial organisms by human beings encroaches on a domain of activity that has been considered to be a God’s divine prerogative (Dragojlovic and Einsiedel 2013). Moreover, how to position the moral status of artificial life, and human beings, as peer life and creator, may confront the challenges of moral status from artificial life. Besides, these creation practices substitute for the natural selection in the evolution process, and lead to new philosophical concerns.

Cluster 3 (blue): Keywords in this cluster primarily related to the ethical concerns of SynBio, especially the potential risk and danger that SynBio may bring about. The high frequency keywords in this cluster are “ethics”, “risk assessment”, “uncertainty”, “ELSI”, “biosafety” and “biosecurity”. The uncertainty of the process of research and practice on SynBio and its products, as well as the risks they may bring about are related to biosafety and biosecurity at the material level. Gómez-Tatay and Hernández-Andreu (2019) tried to distinguish biosafety from biosecurity and “biosafety refers to the prevention of the risks to public health and the environment that could be produced by accidental interactions between dangerous biological agents and other organisms or the environment.” and biosecurity can be defined as “the protection, control and accountability for valuable biological materials [ … ] within laboratories, in order to prevent their unauthorized access, loss, theft, misuse, diversion or intentional release” (WHO, 2006). Biosafety and Biosecurity identified the risks that can be posed by active and passive situations, and turned out to be the major parts of the ethical concerns of SynBio.

Cluster 4 (green): This cluster is basically related to the technologies and upstream science disciplines about SynBio. The high frequency keywords here are “methods”, “gene drive”, “gene editing”, “Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)”; “systems biology”, “biological engineering”, “metabolic engineering” and “agricultural biotechnology”, and the issues about technology such as “patents”, “policy”, “bioeconomy”, “biocrime”, and “bioterrorism”. Systems biology, bioengineering, metabolic engineering, biochemistry and other disciplines and technologies constitute the cornerstone of SynBio. In recent years, the accurate, economical and accessible powerful gene editing technologies like CRISPR and its upgraded versions have provided significant impetus for the leap-forward development of SynBio. In addition, the researches about the technology-related intellectual property and patents (Calvert 2012), as well as policy and regulation issues (Wiek et al. 2012), have also evolved with SynBio.

3.4. RQ4: Potential research trends of SynBio social research

Timezone view of the distribution of literatures’ topics can be used to illustrate the research focus of each period and to show the evolution of research topics and then supply some clues to analyze the potential research trends. In this section, we redistributed and visualized the keywords of collected literatures published in last 5 years in Fig. 5, and switch our focal spots on the latest topics of current field.

Keywords like “public engagement”, “RRI”, “ethics”, “risk”, “biotechnology”, “governance” and so on still have high frequency in the last five years, these issues will not fade out soon as they involve with human beings deeply. However, instead of the four cluster themes analyzed in RQ3 which would dominate the field in the long term and serve as the main stream themes for the next years, here we focus on the three emerging domains that would share some novel perspectives for further research.

(1) New possibilities and challenges brought by SynBio for the transformation of bioeconomy;

The influence of SynBio no longer stays in the fields of basic scientific research or technology development, but has penetrated into the social and economic fields and demonstrated its considerable economic value and commercial potentials. SynBio has been offering possibilities and opportunities for global governments to formulate visions of a transition toward a bioeconomy, and has played the enabling and transformational role of entrepreneurship in bioeconomy (Kuckertz et al. 2020). Moreover, the public engagement access offered by SynBio helps to recruit and train the future workforce for bioeconomy, such as the competition iGEM and citizen science practices (Warmbrod et al. 2020). However, researchers have also noticed the necessary considerations and points of focus in this endeavor owing to the risks and uncertainties of utility in upcoming deployments outside the labs in bioeconomy practices (Parker and Aditya 2020).

(2) The remodeling of SynBio’s multi-dimensional impacts by art

Not many articles discussed the relationship between art and SynBio, but several feasible perspectives have been explored according to the current publications, such as the fusion of art and SynBio in material practice, as well as the reflection on SynBio with artworks. Merritt (2020) used the novel living media interfaces (LMIs) to show the case of the interaction between biological materials and digital systems as responsive living media, and SynBio, as engineered biology, could offer plenty of options for the feasible fusion practice. Vaage (2019) appealed to expand the utility of artworks to provide counter-images to challenge mechanistic assumptions, i.e. the living machines metaphor and the perception of life as controllable in the context of SynBio. Meanwhile, Calvert and Schyfter (2017) argued that “engaging more closely with art and design can enrich STS work by enabling an emergent form of critique”, and “open up the science by exploring implicit assumptions, and interrogate dominant research agendas”. Above all, art offers an interdisciplinary perspective to examine the impacts of SynBio practically and theoretically, and more interaction approaches of them need to be explored.

(3) The role of knowledge of SynBio

The role of knowledge of SynBio has changed since its inception. Its initial form appeared as the knowledge of certain scientific discipline, which was mainly disseminated within the scientific community and then gradually diffused to the public and exerted social influences. In this process, not only the products but also the knowledge itself became the object of ethical research. Therefore, its role has evolved from “knowledge for use” to “knowledge for public communication” and “knowledge as ethical object”. Douglas and Savulescu (2010) put forward the concept of “ethics of knowledge” about SynBio based on the “the misuse of knowledge” and appealed not to regard the creation and dissemination of knowledge of SynBio as granted or beyond doubt. Instead, it called for attention on the risk of misuse of knowledge and advocated for reflection on it as the object of ethical governance, during which its role had been radically changed.

On the basis of Professor Shapira's (2017) research, this paper reconstructed the conceptual system and search strategies of SynBio in order to retrieve the literatures related to it in the sphere of social sciences, and formulated a set of effective retrieval strategies in the social context based on the search result of each related terms. After visualizing the publishing trends in this field, we found that the publications in this field had been growing rapidly since 2006, which encouraged the researchers greatly. In addition, we investigated the top productive countries and regions in this field, which mainly consisted of the developed world. The United States and the United Kingdom had the top two highest numbers of publications, which contained several prolific research teams from the universities in regions such as Edinburgh and Manchester. But this kind of cooperation was basically within the institutions, the inter-institution cooperation was less significant here.

The research areas of collected literatures involved with philosophy and ethics mostly, such as history and philosophy of science, ethics, philosophy, medical ethics, etc. In addition, communication, environmental studies and other social sciences also took a certain proportion, which implied the diversity of research themes about SynBio in social context.

After that, we investigated the intellectual base of current field and the high frequency co-cited references and found that knowledge source of natural sciences and social sciences took the dominant places on the earlier and later stages separately. With cluster analysis and visualization technology, co-cited reference network was generated and visualized to find the three representative stages of knowledge background and the research topics of each stage, namely, knowledge transfer, public engagement and diversified reflection. Sources title of collected literatures were also listed to help researchers follow the progress and development of this field.

In RQ3, we tried to identify hotspots in this area with co-word methodology, and managed to cluster the keywords into four domains, and introduced the theme of each domain. These hotspots could help to locate the research fronts in the current field, to access to the novel ideas, and to systematically understand the development of the field. Finally, we extracted and visualized the network of keywords in last 5 years, and tried to find out the potential research trend and identified the three novel research domains, which might inspire the researchers and stakeholders.

COVID-19, the ongoing overwhelming pandemic, and other pandemics i.e. SARS, H1N1, H5N1, MERS in recent years, even the deterioration of public opinion on genetically modified foods have shattered people’s confidence over biotechnologies and the institutions. To respond to such emerging crisis requires the cooperation of natural science scientists, government officers and regarding citizens [23]. In these unexpected emerging situations, SynBio can benefit the treatment of infectious diseases and the development of vaccines. Therefore, in such a complex situation, how to release the positive potentials of SynBio, avoid the risks and dangers it might bring to the world by institutionalized means, explore appropriate ethical rules and policies to accelerate the benign development of SynBio and benefit human beings has become an inescapable issue. And COVID-19 just magnifies the urgency. Thus in addition to the natural science researches, social sciences, philosophy and ethics also need more attention to do research in advance before the possible events.

In this study, we constructed a novel conceptual framework and search strategy about SynBio in the context of social sciences, and systematically reviewed the relevant literatures in this field with the mature and well-proved methods such as co-occurrence analysis and knowledge mapping. We also illustrated and clarified the literatures from three aspects: hotspots, potential research trend and intellectual base. This study aims to provid relevant researchers, policy makers and skate holders with a complete knowledge system to follow the development of SynBio.

However, this study also has its limitations. For example, about data source, only the records from SSCI and A&HCI index were collected in this study, while other databases were excluded, even for the purpose of ensuring the impact and authority of literatures. For further research, on the one hand, the sub-areas such as the ethics or philosophy can be worthy of further study to explore enlightening ideas. On the other hand, the potential trends proposed in this paper have pointed out possible directions for further research.

Ethics approval: Not applicable

Consent for publication: Not applicable

Consent to participate: Not applicable

Availability of data and material: Data will be available on reasonable request by corresponding author of the manuscript (Dr Dong Wang [email protected])

Conflict of Interest: the manuscript holds no conflict of interest among all contributing authors.

Funding Acknowledgement: The research is funded by Fundamental Research Funds for the Central Universities (YD2110002004 and YD2110002014)

Author contribution: Conceptualization – QK; Formal analysis – DW; Funding acquisition – GW; Investigation – QK; Methodology – FA; Software – DW; Supervision – GW; Validation – GW; Visualization – FA; Writing - QK; Writing - review & editing – QK and DW

Acknowledgement: Authors would like to thank Prof. Zhou Rongting for support.

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No competing interests reported.

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Ethical and Social insights into Synthetic Biology: Bibliometric approach and predicting research fronts in POST-COVID-19 era

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Version 1

Abstract

Figures

Highlights

1. Introduction

2. Methodology

2.1. Bibliometrics, Co-occurrence Analysis and Visualization

2.2. Data collection

3. Empirical Results

3.1. RQ1: Literatures Distribution

3.1.1. Most productive countries and institutions

3.1.2. Research areas

3.2. RQ2: Intellectual bases of current field

3.2.1. Highly co-cited references related to SynBio in social sciences

3.2.2. Intellectual bases: Cluster analysis of co-cited references

3.2.3. Highly co-cited journals

3.3. RQ3: Hotspots in SynBio related literatures in social sciences

3.4. RQ4: Potential research trends of SynBio social research

4. Discussion

5. Conclusion

Declarations

References

Competing Interests

Status:

Version 1