SynBio1: Introduction to synthetic biology (v1.0)

The key references for synbio series are Wikipedia and other internet sources and Prof Milton Muldrow of Wilmington University. 

This is the first essay on the new field of synthetic biology. Until recently all life forms were the handiwork of nature. But mankind has slowly mastered the science of creating new lifeforms or adapting existing ones. This essay introduces this subject. To those religiously inclined, is man evolving into a "god"? Not really. Man is very heavily copying and learning from nature/god's work. Man did not invent or design or create the fundamentals of biological systems in the first place. Nature/God did. 

Synthetic biology (SynBio) is a multidisciplinary field of science that focuses on living systems and organisms, and it applies engineering principles and molecular methods to develop new biological parts, devices, and systems/life or to redesign existing systems/life found in nature. It is a branch of science that encompasses a broad range of methodologies from various disciplines, such as biotechnology, biomaterials, material science/engineering, genetic engineering, molecular biology, molecular engineering, systems biology, membrane science, biophysics, chemical and biological engineering, electrical and computer engineering, control engineering and evolutionary biology. 

Engineers view synthetic biology as technology (in other words, a given system includes biotechnology or its biological engineering). Synthetic biology includes the broad redefinition and expansion of biotechnology, with the ultimate goal of being able to design and build engineered live biological systems that process information, manipulate chemicals, fabricate materials and structures, produce energy, provide food, improve environment, and maintain and enhance human health, as well as advance fundamental knowledge of biological systems and our environment. Researchers and companies working in synthetic biology are using nature's power to solve issues in agriculture, environment, manufacturing, and medicine.

Some key milestones are: 

1973: First molecular cloning and amplification of DNA in a plasmid is published in P.N.A.S. by Cohen, Boyer et al. constituting the dawn of synthetic biology. 

1978: Arber, Nathans and Smith win the Nobel prize in Physiology or Medicine for the discovery of restriction enzymes, leading Szybalski to offer an editorial comment in the journal Gene: "The work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes, but also has led us into the new era of synthetic biology where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated." This was a foundational advance!!

1988: First DNA amplification by the Polymerase chain reaction (PCR: Covid-19 tests are PCR tests) using a thermostable DNA polymerase is published in Science by Mullis et al. This obviated adding new DNA polymerase after each PCR cycle, thus greatly simplifying DNA assembly. This was a foundational advance!!

2003: The most widely used standardized DNA parts, BioBrick plasmids, are invented by Tom Knight. These parts will become central to the International Genetically engineered Machine (IGEM) competition founded at MIT in the following year. This was a foundational advance!!

2004: First international conference for synthetic biology, Synthetic Biology 1.0 (SB1.0) is held at MIT.

2010: Researchers publish in Science the first synthetic bacterial genome, called M. mycoides JCVI-syn1.0. The genome is made from chemically synthesized DNA using yeast recombination.

2012: Charpentier and Doudna labs publish in Science the programming of CRISPR-Cas9 for genetic editing. This technology greatly simplified and expanded eukaryotic gene editing. They received the 2020 Nobel prize in Chemistry for this work. It was a foundational advance!!

2019: Scientists at ETH report the creation of the first bacterial genome, named Caulobacter ethensis-2.0 made entirely by a computer, although a related viable form of C. ethensis-2.0 does not yet exist. Researchers also report the production of a new synthetic form of viable life, a variant of the bacteria Escherichia coli, by reducing the natural number of 64 codons in the bacterial genome to 59 codons instead, in order to encode 20 amino acids.

2020: Scientists created the first xenobot (tiny machines made out of living parts), a programmable synthetic organism derived from frog cells and designed by AI. They could move, work together and self-heal. In 2021, Scientists reported that xenobots are able to self-replicate by gathering loose cells in the environment and then forming new xenobot. This was a foundational advance!!

The field has continued to advance rapidly since. 

Due to more powerful genetic engineering capabilities and decreased DNA synthesis and sequencing costs, and increased availability of massive computational power and AI, the field of synthetic biology is rapidly growing. In 2016, more than 350 companies across 40 countries were actively engaged in synthetic biology applications. In synthetic biology, biological cells and processes are dismantled and reassembled to make novel systems that do useful things. It has two main subfields. One uses unnatural molecules to reproduce emergent behaviors from natural biology, with the goal of creating artificial life. The other seeks interchangeable parts from natural biology to assemble into systems that act unnaturally.

 Some of the companies to keep an eye on are: 

  • Ginkgo Bioworks (MA. Therapeutics, food/agriculture, vaccines, bio security, flavor/fragrance)
  • Bolt Threads (CA. materials/fashion and beauty)
  • Mammoth Biosciences (CA. Therapeutics)
  • LanzaTech (IL. Carbon recycling)
  • Motif FoodWorks (MA. Food)
  • Joyn Bio (MA. Agriculture)
  • Kiverdi (CA. Meat, Agriculture, fishery, ocean plastics, carbon recycling)
  • Perfect Day (CA. food)
  • Viridos (CA. sustainable technology)
  • Upside Foods (CA. food)

Think tank BCG Henderson Institute projects the meat, beauty and pharmaceuticals industries are on the brink of being taken over by synthetic biology; and the agriculture, automobile and fashion industries will follow soon after. Longer term, the momentum gained in this space stands to transform more than just a handful of industries, though, essentially impacting the entire economy. Synthetic biology holds great promise for addressing global needs. However, many current developments are not immediately translatable to ‘outside-the-lab’ scenarios that differ from controlled laboratory settings. Challenges include enabling long-term storage stability as well as operating in resource-limited and off-the-grid scenarios using autonomous function. 

There are risks, however.  In 2018, a Chinese researcher, He Jiankui, altered the DNA of newborn twins with gene editing (to add immunity to HIV) without proper oversight and approval, and this kind of research poses a unique danger (Jiankui went to a Chinese prison). Also gain of function research on pathogens which is quite widespread but controversial (related but a distinct field from SynBio) are another danger point if these engineered pathogens are intentionally or inadvertently released potentially triggering a pandemic. There are not yet adequate laws to put guardrails on this and related disciplines. 



Comments