Applications and Challenges for Employing Synthetic Biology in Public Health
Seoyun Lee, Daegu International School, Dong-gu, Daegu, Republic of Korea
From novel anticancer therapy to next-generation Sustainable Development Goals (SDG) products, genetic parts and biological building blocks of synthetic biology have evolved into memory elements, pulse generators, digital logic gates, etc. Advances in synthetic biology exploit small gene networks to bring electronics-inspired behaviors in more extensive biological programs with the integration of synthetic biosensing circuits and biosensor-sensitive elements - plasmid design. Hence, it contributes to drug-target identification, drug-discovery platforms, disease treatment, and drug access unrealizable by traditional genetic and metabolic efforts – namely regulated, site-specific, and optimized (Lee & Na, 2013). With constantly renewed interest in pathway components and hybrid solutions, synthetic biology aspires to design a sophisticated, automated, and multitasking “organism” summoning virtues of biocomputing. Multidisciplinary approaches in synthetic biology, such as long-term storage, operationalized biotechnology, and digital signal detection, demonstrate resolution to on-demand challenges, namely space missions, disease outbreaks, and bioremediation (El Karoui et al., 2019).
Case A: Synthetic Biology in Next-Generation Medicine
Cancer is one of the most dreaded diseases in humans in the twenty-first century: a conservative estimate reports 19,290,000 novel cases (3.2% of the global population, of >15 nomenclature) in 2020 alone (Sarotra & Medhi, 2016). Despite the strict implementation of conventional chemotherapy, radiation, surgery, and clinical research accruing to $895 billion, a 5-year survival rate of 5~25% is reported (“Financial Burden,” n.d.). To date, treatment modalities ensure side effects costly to public health -- worst grade elements and recurrence, for instance -- owing to inherent cytotoxicity and lack of specificity (Pearce et al., 2017). To combat these hallmarks, Zheng and colleagues engineered a strain of S. typhimurium (selectively targeting the hypoxic tumor microenvironment) to over-express flagellar protein Vibrio vulnificus flagellin B (FlaB), which activates host immune response via Toll-like receptor 5 and 4 (TLR5/4) pathways upon sensing tumor microenvironment. Adaptive immune response activates leukocyte neutrophils and macrophages to “infiltrate” neoplasia and secrete tumor necrosis factor 𝛂 (TNF-𝛂) and interleukin 1𝛃 (IL-1𝛃), inflammatory chemokines that further anticancer activity (Zheng & Min, 2016).When adequately industrialized, bacterial antineoplastics may render a novel cancer therapy on a global magnitude, minimizing exorbitant cost, intrusiveness, and worst grade elements of cancer treatment. Inducing bioavailability and applicability via personalization, “bad-rap” bacteria may pioneer a pathway to a medical breakthrough (McNerney et al., 2021).
Case B: Synthetic Biology in Sustainable Development Goals
Forest fires harm ecological niches and human safety: mountain chains, suiting a heterogeneity of endemic plants, root ecological significance of continental territories. However, the use of conventional firefighting foams ensures both economic and environmental costs -- expanding to population-wide ophthalmological and respiratory irritation when inadequately applied (Finlay et al., 2012). A research team at Facultad de Ciencias Biologicas pioneered the first synthetic biology-based firefighting foam to combat this issue. Inspired by frog-derived Ranaspumin proteins – the most efficient foaming compound reported in the literature – the team attenuated a strain of E.coli to produce Rsn-2, Rsn-3, Rsn-4, and Rsn-5 as primary surfactants and stabilizers with non-polar N-terminal sequence. As a secondary foaming agent, synthesized surfactin held promising water surface-tension reducing properties imperative for firefighting. Also, purified Ranaspumin and surfactin were homogenized with a biofilm of Bacillus subtilis to stabilize the foam by preventing oxygen or water influx (“Team:FCB-UANL/Description,” n.d.). By obtaining synthetic means of mass production with ensured safety and biocompatibility when aggregated, the team fulfilled SDG (a global partnership initiative to ameliorate education, health, and the environment worldwide) #9 (industry, innovation, and infrastructure) and #15 (life on land) issued by the United Nations (UN) (“THE 17 GOALS,” n.d.). Industrial scaling up with local firefighting agencies is called to ensure public welfare further.
Current Limitations in Academia
Despite its futuristic significance, there are many impediments to successfully implementing synthetic biology in real life. Priority of research effort often reflects value judgments and cost-benefit calculations of stakeholders, which differs from general preferences of the society and generates gaps between clinical research and medical decision making. Because characteristics and comorbidities of clinical research hold less resemblance to clinical practice, limited involvement of clinical physicians also serves as a barrier to translating evidence-based practices to clinical practice (Jones & Platts-Mills, 2012). Clinical investigators without community physicians find clinical review cycles (obtaining IRB approvals, securing material transfer with stakeholders and medical centers, and securing informed consent) difficult and drop out after the first trial (Morris & Ioannidis, 2013).
Indeed, orthodox biology has proven deficient in addressing the novelty of issues emerging in the 21st century. Hence, demand for a paradigm shift has risen. Enter synthetic biology – field of biology redesigning organisms for valuable purposes by engineering them to have novel abilities. Albeit promising in devising an accessible, applicable, and problem-oriented “machine” unrealizable with chemical-based mediations, current systematics of the academia must be redressed for synthetic biology to yield its potential in real life. As its versatile application in real-life contexts and the “evolving” nature of field promise, synthetic biology is a powerful solution to revolutionize the scratchpad in which science interplays with life.
Jones, C. W., & Platts-Mills, T. F. (2012). Understanding commonly encountered limitations in clinical research: an emergency medicine resident’s perspective. Annals of Emergency Medicine, 59(5), 425-431.e11. https://doi.org/10.1016/j.annemergmed.2011.05.024.
McNerney, M. P., Doiron, K. E., Ng, T. L., Chang, T. Z., & Silver, P. A. (2021). Theranostic cells: emerging clinical applications of synthetic biology. Nature Reviews. Genetics, 22(11), 730–746. https://doi.org/10.1038/s41576-021-00383-3.
Pearce, A., Haas, M., Viney, R., Pearson, S.-A., Haywood, P., Brown, C., & Ward, R. (2017). Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study. Plos One, 12(10), e0184360. https://doi.org/10.1371/journal.pone.0184360.