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Advancements and Ethical Considerations in Synthetic Biology
The ultimate questions for a synthetic biologist are thus: Can we endow cells with life-enhancing functions and ultimately improve the human condition? Should cells be considered property and can they be patented? Should biological production via synthetic methods be allowed and if so, what are the financial rights of the inventor, the producers, and the consumers? These are questions of ethics, economics, and public policy. There are incredibly promising advancements in synthetic biology. There are also a large number of areas that specialists, ethicists, regulators, and policymakers, not involved in the research, need to address.
Sidney W. Fox, Ph.D., began his biochemistry career with the goal of reducing metabolic pathways within cells to their most primitive forms – although he did not have the words to refer to this as synthetic biology goals. However, Fox’s stated aim has always been to convince nature to build a cell de novo. Time, considerable elucidation of metabolism, biophysics, and biochemistry skills were all that stood in between Fox and this simple yet incredibly difficult challenge. Sidney Fox has spent nearly 40 years working towards the moment when sufficiently simple, life-giving conditions could be created to allow him to “kick-start” life. Dr. Fox ultimately postulated that the first genetic material was indeed produced by naturally occurring abiotic chemistry, perhaps delivered by comets to form the first genetic molecules.
Understanding life through DNA sequencing: Arguably the most impactful advancement in the field of synthetic biology is DNA sequencing and the downstream sector of genetic engineering. The mapping of the 3.2 billion nucleotides of the human genome ushered in the era of “big biology”, with the cost of whole-genome sequencing falling from dollars in 2007 to the verge of pennies before the end of the current decade. The exquisite enrichment of biologically relevant subunits in this comprehensive view of cellular activity has been nothing short of transformative for the entire biological landscape.
The Obvious: Genes and Pathways: Genetic editing, either with extensions of acquired immunity, as seen in CRISPR/Cas, or other platforms like TALENs and zinc finger nucleases, have made the manipulation of unrealistic fantasy into routine practice. The placement of transgenes, be them fluorescent locators, switches or over-and under-expressors, can inform on construction and, importantly, validate observations on cellular biology. Naturally, there is a locomotion towards more pre-constructed pieces for insertion and function that do not require custom preparation, insertional testing or high maintenance due to leakage of activity. Competitive platforms like BioBricks and freestanding search themes will be bred for this hunger to be sated with plug-and-play assembly of DNA strands that function as precisely as ordered. This process of interpolation, yet largely poorly documented, has enabled whole pathways and even genomes to be written that enable and execute cellular activities. The least of the accomplishments is the interfacing and template to assess function and figure out pathways. All of this mass crunching in large-scale bioinformatics deals, impressive as they are in biological system interpretation, are reluctantly smirched by downstream devolutions that are required for the biological end modification.
Enzymatic Platforms: Problems Solved, or Just Begun? There will always exist an interface between largely decomposed molecular biology information and atomic-scale mechanistic detail. Many productive avenues exist for progress, as seen in efforts to connect pathway knowledge with the superfamily of transporters related to antibiotic resistance. Another possibility, an extension of binding proteins of the molecular glue perspective of designed allostery, is the mapping between the genetic things that are instructed and their controlled assembly—enzyme complexes, storage proteins, or microbial body shells, like the cage of ferritin—into hypothetical organelles.
Devices of the Future: Electronic Genetics. The ultimate construction of pathways and biological systems involves reversibility, switching, logic tests, and syncopated release. Collectives of this eventuality, as evolved entities that can self-activate and self-repair, represent hardware of the future. Are these next steps in evolutionary pathways, at least, the Solid Nature phase of DNA origami, like the Hauptmann and Zabeau proposal to implement DNA as logic rather than just memory, might transition from the present-day idea of manipulating and improving that is redolent in the fix of impersonal operations. The digital control of distributed devices we now couple to the sometomes register result shards form circuits in the ununixce of cyberspace offers prelude. How do we harness and control computation that obeys the behaviors of biological cells to both improve life and better understand it? These open concepts, as beguiling as an artificial nucleoprotein pitch that cooks its own recipe in pavement, cannot be further understood without deeper insight into interface limitations, which more often than not are not biological in nature.
In addition to the generation of economic growth, applications of synthetic biology in various fields have the potential to address some of the most pressing issues of our times, from the sustainable production of environmentally friendly materials and the treatment of pollutants, to the development of new and improved biofuels, the delivery of novel treatments for antibiotic-resistant and non-communicable diseases, and the provision of diagnostic tools for the early detection and monitoring of these and other illnesses. Social and ethical concerns surrounding the field are also beginning to be recognized, by some at least. However, despite recently announced global investment of at least $10bn in synthetic biology research and development, the field’s potential impacts on society have been little discussed.
For sure, most synthetic biologists are committed to acting responsibly. It is frequently pointed out that the field has produced many ‘aspirational’ visions, such as that of a low-carbon and sustainable economy, a healthy population immune to the threat of disease, and the offering of treatments for those currently neglected by traditional biotech and pharma. In addition to these, we argue, it is crucial for the synthetic biology community to ensure that the fruits of its labor do not contribute to, or exacerbate, global inequalities: within societies, between countries, and between the present and generations to come. Fully and candidly debating the societal implications of their research should not just involve synthetic biology’s scientists, entrepreneurs and investors, but also politicians, policymakers, the general public, and the specific communities – both inside and outside academia – that may be affected. This endeavor can only increase the likelihood that the beneficial applications of synthetic biology are developed to the full and that its negative impacts are either removed or mitigated.
Synthetic genomics integrates scientific research that contributes to areas such as biotechnology, genetics, and epigenetics. It merges knowledge from those areas and from biomedicine, computational biology, pharmacognosy of natural products, and bio-renewable chemical products. It would use both rational design methods and the in vitro chemical synthesis of DNA, including entire genetic circuits, full-length genes, and complete synthetic genomes in order to install into cell lines as additional chromosomes. Essentially, synthetic biology can be seen as an extension of the field of medical biotechnology (genetic pharmacological biotechnology) and pharmacognosy of natural products. In particular, synthetic genomics uses chemically synthesized genes, in vitro gene assembly, and chemical synthesis of genomes which bypass many of the time- and work-intensive protocols of current genetic engineering methods, in order to add functional hereditary information to recipient organisms that have a markedly reduced (or absent) reorganized recipient genetic background.
Other realistic applications of synthetic genomics are in increasing the biotechnological content of cell-based methods of transfecting cell lines with large amounts of foreign DNA and to allow for high stacking of DNA-infected cell lines. This information may then be caused to be lost through the combined practice of ethical endo-soma for genome remnants and neuromuscular differentiation. This attribute may then further be used to harvest from the generated cell populations.
Synthetic biology, like many rapidly moving fields, is difficult to define or pinpoint in terms of what the cutting-edge projects, trends, and ideas are at present. One increasingly important concept within the field is that it no longer solely concerns the creation of new systems, devices, or processes, but is merging with outright engineering (often interchangeably used with design) of biology. The recasting of biologists and genetic engineers as synthetic biologists is tied in part to the complete recasting of biology as a subject; DNA is increasingly seen as a modular construction system, consisting of standardized and interchangeable parts, allowing us to skip blandishments of what is present in favor of building ab initio the ingredients of life.
The revolution in DNA sequencing has already had profound effects across the life sciences, becoming far faster, easier, and cheaper over just a few short years. In doing so, it has also fundamentally shaken up ideas of where synthetic biology begins: does it begin with reconstructing and reprogramming extant biological systems or creating new life based on new genetic code? There is also an increasingly felt need to create more high-throughput methods for characterizing artificially designed genes and reengineered biological systems. These will aid in conducting both ex situ and in vivo experiments. Such tests for functionality are paramount when constructing genomes or parts thereof from scratch. Raw power opens up much more than an ability to ask more detailed questions about the known; the pursuit of diversity, with its open-ended questions and potential novel discoveries, has reshaped the direction of basic research in many other scientific fields.
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