Raphael Thys
Synthetic biology is an overarching category of science that encompasses everything from genetic engineering to creating new biological structures using 3D printing. It can be seen as involving any imaginable way of redesigning — or even repurposing — organisms and parts of organisms to have new features and functions. The myriad problems that abound in health & medicine, agriculture, environmental disasters, and even manufacturing present virtually limitless opportunities synthetic biology has to offer solutions.
From the cell, molecular, genetics, and systems, every subfield of biology contributes to synthetic biology’s toolkit that empowers new enzymes, biological systems, metabolic pathways, genetic circuits, and more. An apt analogy might be to compare synthetic biology to computer systems design. The focus begins with small core components and evolves into large interrelated systems that must work in tandem with other external systems and assemblies. However, much of the similarity stops there. While technological engineering is well understood and within nearly total control by humans, biology is far more complex and unpredictable. Changes made to a single gene that’s been mapped to a phenotypic trait like eye color may have unknown consequences as the development of an organism plays out in its entirety, resulting in mutations that are either harmful more often than not or neutral.
The Engineering Biology Research Consortium (EBRC) states that there are four main pillars to synthetic biology:
“1)…the scientific idea that one practical test of understanding is an ability to reconstitute a functional system from its essential parts. Scientists are testing models of how biology works by building systems based on models and measuring differences between expectation and observation using synthetic biology.2)…biology is an extension of chemistry, and thus synthetic biology is an extension of synthetic chemistry. Attempts to manipulate living systems at the molecular level will likely lead to a better understanding and new types of biological components and systems.
3)…the concept that natural living systems have evolved to continue to exist, rather than being optimized for human understanding and intention. By thoughtfully redesigning biological living systems, it is possible to test our current knowledge simultaneously. It may become possible to implement engineered systems that are easier to study and interact with.
4)…biology can be used as a technology (biotechnology) that includes the engineering of integrated biological systems for processing information, producing energy, manufacturing chemicals, and fabricating materials.”
Synthetic biology is still more of an emerging field than a mature one because there is still much to learn in two of the primary technologies that enable it: DNA sequencing and DNA synthesis. Tremendous advances have been made in both capabilities in recent years, but synthetic biology’s ultimate value hinges directly on their continued progress.
The worldwide synthetic biology market is estimated to be worth nearly $24B by 2025; however, relatively little is being invested. Annual investments in synthetic biology in the United States — the country investing the most — hover below $200 million. Quadrupling that investment is within easy reach, and seems like an outstanding deal considering more research and development, yielding more use cases and products, could likely grow the market to $100B.
The largest potential segment of that sizable market will be dedicated to improving human health and increasing human longevity, especially as the world’s population continues to skew older. With every year that goes by, the global ratio of people over age 65 to those under grows greater. This skew to those aged 65 and over has been long understood to be caused by increased access to better nutrition and medical care as nations progress through developing status and on into first-world (or near-first-world) living conditions.
One of synthetic biology’s biggest miracle-workers is the humble yeast. These simple, single-celled fungi possess protein secretion pathways that are remarkably like those in higher-order multicellular creatures. Yeast is an ideal microscopic “factory” in which to generate the kind of recombinant proteins that synthetic biologists can use in many applications. In a study published in March 2020, researchers looked at a wide range of possibilities, including:
“…new genetic tools for optimizing secretory protein expression, such as codon-optimized synthetic genes, combinatory synthetic signal peptides and copy number-controllable integration systems, and the advanced cellular engineering strategies, including endoplasmic reticulum and protein trafficking pathway engineering, synthetic glycosylation, and cell wall engineering, for improving the quality and yield of secretory recombinant proteins.”
Saccharomyces cerevisiae cells (brewers’ yeast) under an electron microscope. © NASA
Biomedicine — the hybrid field that deals with manipulating fundamental factors of living tissues in order to generate new therapies and treatments — is seeing significant progress due to synthetic biology. In turn, this will change healthcare for the better, moving into the future. There are a dizzying number of exciting studies to illustrate synthetic biology’s power:
- Wireless diagnostics might be used to control insulin dosing via the interfacing of living cell tissues with computers (aka a synthetic control system) in what is being called “cybergenetics.”
- Metabolic pathways can be designed that alter barely noticeable molecules such as biomarkers of various cancers to become detectable.
- Unique theranostic cell lines (named after radioactive drugs that are used in combination to both detect and treat cancers) that find disease and respond to kill it.
- The Human Genome Project — GP Write project aims to craft complete human chromosomes and renew focus to create a chromosome resistant to viruses, including over 400,000 alterations to the human genome that will cripple viral avenues of attack.
- Our gut microbiome will be engineered to yield new probiotics.
- Special pigs with immune systems compatible with humans will be engineered to allow true xenotransplantation.
- Synthetic biology is paving the way for methods that might allow geneticists to engineer a patient’s cells, reprogramming them into a new form of stem cell that could then be directed to repair tissues as needed.
- Genetically-engineered viruses and human T-cells are already in use to help correct inherited diseases and destroy cancer cells.
These fantastic advances are just a few examples of the engineering capabilities that are of such profound importance to synthetic biologists. Two other critical tenets of synthetic biology involve looking for ways to innovate on biological systems or replicate biological processes where they might perform a useful function. One example of the latter is known as CR mimetics: utilizing biochemical pathways to recreate the effects that calorie restriction is known to boost maximum lifespans in lab organisms like the flatworm C. elegans. One such CR mimetic that is known to be effective in C. elegans is the polyphenol compound resveratrol, which reduces the decline in mitochondrial function that comes with age. Whether resveratrol works in any measurably similar way in humans is still awaiting conclusive evidence, but research continues on other CR mimetics.
Synthetic biology ultimately represents the full promise of genetic engineering and biomedicine combined. With this comes all of the possible concerns related to the safety of the resulting therapies and procedures and the ethical dilemmas inherent in such a world-changing field. For every credible research lab — in the quest for disease cures and anti-aging therapeutics — there are likely covert or clandestine labs with selfish or sinister aims that might be dabbling in the dark waters of eugenics or biological terrorism.
One way to help combat synthetic biology research’s shady side is to provide more support to those who work in the light. Institutions of higher learning and science-minded organizations need to give time and energy and drum up financial support via any nonprofit arms they may bring to bear. Venture funds with vision need to step forward to help startups and founders with powerful ideas get the funding and leadership to grow. One of these funds is SP8CEVC, run by partners Capt. Franz Almeida and Junaid Mian, RPh. Their vision fuses the intersection of human longevity research with the emerging space economy and the realization that living and working in space will require humans to be protected by a biomedical technology level never before seen — a goal that only synthetic biology can achieve.
Envision a not-so-distant future in which a 90-year-old astronaut, still in the prime of her life, is the first human to set foot on a planet in another solar system.