Synthetic Biology: The Technology of Life

Published October 26, 2023

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Intro

During a recent US trip, I picked up “The Coming Wave” by Mustafa Suleyman. The book is about two technologies – Artificial Intelligence and Synthetic Biology. Mustafa dubs them as the technology of intelligence and the technology of life, respectively. He (or rather AI) writes in the prologue:

In the annals of human history, there are moments that stand out as turning points, where the fate of humanity hangs in the balance. The discovery of fire, the invention of the wheel, the harnessing of electricity—all of these were moments that transformed human civilization, altering the course of history forever.

And now we stand at the brink of another such moment as we face the rise of a coming wave of technology that includes both advanced AI and biotechnology. Never before have we witnessed technologies with such transformative potential, promising to reshape our world in ways that are both awe-inspiring and daunting.

On the one hand, the potential benefits of these technologies are vast and profound. With AI, we could unlock the secrets of the universe, cure diseases that have long eluded us, and create new forms of art and culture that stretch the bounds of imagination. With biotechnology, we could engineer life to tackle diseases and transform agriculture, creating a world that is healthier and more sustainable.

But on the other hand, the potential dangers of these technologies are equally vast and profound. With AI, we could create systems that are beyond our control and find ourselves at the mercy of algorithms that we don’t understand. With biotechnology, we could manipulate the very building blocks of life, potentially creating unintended consequences for both individuals and entire ecosystems.

The book is about the promise and perils of the two technologies, and the need for containment. Writes Mustafa: “The coming wave is defined by two core technologies: artificial intelligence (AI) and synthetic biology. Together they will usher in a new dawn for humanity, creating wealth and surplus unlike anything ever seen. And yet their rapid proliferation also threatens to empower a diverse array of bad actors to unleash disruption, instability, and even catastrophe on an unimaginable scale. This wave creates an immense challenge that will define the twenty-first century: our future both depends on these technologies and is imperiled by them.”

Around the same time, I came across another book, “Programmable Planet”, by Ted Anton. From its description:

A new science is reengineering the fabric of life. Synthetic biology offers bold new ways of manufacturing medicines, clothing, foods, fragrances, and fuels, often using microbe fermentation, much like brewing beer. The technology can help confront climate change, break down industrial pollutants, and fight novel viruses. Today, researchers are manipulating life forms and automating evolution to create vegetarian “meat,” renewable construction materials, and cancer treatments. In the process, they are changing our concept of what life science can achieve. Is this a new industrial and information revolution—or dangerous tinkering that could unleash unintended consequences?

Programmable Planet is a grand tour through the world of synthetic biology, telling the stories of the colorful visionaries whose ideas are shaping discoveries. Ted Anton explores the field from its beginning in fighting malaria in Africa to the COVID vaccines and beyond. Covering medical and agricultural triumphs and blunders, he examines successes in energy production, plant gene editing, and chemical manufacturing, as well as the most controversial attempts at human gene enhancement. This book reports from the front lines of research, showing policy makers’ struggle to stay abreast of the technologies they aim to regulate. Even-handed, lively, and informative, Programmable Planet gives a glimpse of the promise and problems of a new biology-based industry.

What intrigued me was ‘synthetic biology.’ I had heard the phrase for the first time a few months ago. (While my world is centred around marketing tech, I do like to explore new technologies.) The reason I have woken up late to the synthetic biology revolution is that I never liked biology. I stopped studying it at the earliest opportunity – right after tenth grade. I preferred to go to St. Xaviers College in Mumbai in the 11^th rather than Jai Hind because biology was not compulsory in Xaviers. I opted for Geology. Having seen the phrase on more than a few occasions, my curiosity took over. I decided I needed to understand it more, and the best way to learn for me is to read and write. Hence this blog series.

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What It Is

My first stop was to query ChatGPT and ask what synthetic biology is and its core technologies. Here’s what I got.

Synthetic Biology is an interdisciplinary field that combines principles from biology, engineering, computer science, and other areas with the aim to design and construct new biological parts, devices, and systems or to redesign existing natural biological systems for useful purposes. It seeks to create new biological functions that do not exist naturally and offers a more systematic approach to engineering biology.

Here’s a breakdown of its significance:

1. Understanding Fundamental Biology: By attempting to recreate biological systems, scientists gain deeper insights into the principles that govern life. This helps us understand the complexity and nuances of living organisms.
2. Medical Applications: Synthetic biology has the potential to revolutionize medicine. For example:

1. • Personalized Treatment: Tailored therapies based on an individual’s genetic makeup.
   • Drug Synthesis: Microorganisms can be engineered to produce drugs, reducing the need for chemical synthesis.
   • Targeted Therapies: Design of microorganisms that target cancer cells or other disease-causing agents without affecting healthy tissues.

3. Sustainable Production: Organisms can be engineered to produce fuels, chemicals, and materials in more sustainable ways than conventional methods. For instance, bacteria might be modified to produce biofuels from waste products.
4. Environmental Remediation: Synthetic organisms can be designed to break down pollutants or absorb heavy metals, helping to detoxify environments that have been subjected to industrial pollution.
5. Food and Agriculture: By modifying crops or creating new organisms, we can produce food that is more nutritious, requires fewer resources, or is more resistant to pests and diseases.
6. Bio-computing: DNA and other biological systems have been explored as potential mediums for computation and data storage, presenting a whole new paradigm for computing.
7. Safety and Biosecurity: On the flip side, synthetic biology has implications for biosecurity. While it provides tools to address global challenges, there’s also a risk of misuse, either accidentally or with malicious intent. Thus, the field underscores the need for stringent safety and ethical guidelines.

Core Technologies

Synthetic biology is propelled by a range of core technologies that enable scientists to design, construct, and test biological systems in more standardized and engineering-like ways. Here are some of the foundational technologies:

1. DNA Sequencing: This allows us to read the genetic code of organisms. Rapid advances in sequencing technologies have made it faster and cheaper to read DNA, providing vast amounts of genetic data to researchers.
2. DNA Synthesis: Once the desired DNA sequence is known, it can be custom-made using chemical methods. Advances in DNA synthesis technology enable scientists to create long strands of DNA with custom sequences, which can be inserted into organisms to introduce new functions.
3. Gene Editing: Technologies like CRISPR-Cas9 allow scientists to make precise changes to an organism’s DNA. This has revolutionized synthetic biology by allowing for more accurate and efficient modifications.
4. Bioinformatics and Computational Biology: These involve using computer algorithms and software tools to design and model biological systems. Computational tools can predict how changes in DNA will affect an organism’s function, enabling more precise engineering.
5. Standardized Biological Parts (BioBricks): Just as electrical engineers use standard parts (like resistors and capacitors) to build circuits, synthetic biologists aim to create libraries of standardized biological parts (like promoters, genes, and terminators) that can be mixed and matched to build new biological systems.
6. Automated DNA Assembly: Automation platforms, like robotic systems, allow for the rapid assembly of multiple DNA parts in a precise order, accelerating the construction of synthetic biological systems.
7. Microfluidics: This involves manipulating small amounts of liquids on a chip. Microfluidics can be used for high-throughput testing of biological samples, greatly speeding up experiments.
8. Protein Engineering: This focuses on designing new proteins or modifying existing ones to have desired functions. Techniques like directed evolution, where proteins are evolved in the lab under artificial selection pressures, can create proteins with novel or improved functions.
9. Synthetic Genomes: Scientists are working on creating entire synthetic genomes. The first synthetic bacterium with a completely synthetic genome was reported in 2010. Such approaches might lead to organisms that are entirely human-designed.
10. Metabolic Engineering: This involves redesigning the metabolic pathways of an organism, often to produce a desired chemical or compound. For instance, yeast cells have been engineered to produce biofuels or antimalarial drugs.
11. Chassis Organisms: These are simple, well-characterized organisms that synthetic biologists use as platforms for adding new functions. Examples include certain strains of E. coli bacteria, which are often used because their genetics are well understood.

These technologies, combined with principles from engineering, are what allow synthetic biologists to approach biology in a modular and systematic way, designing organisms to carry out desired tasks. As with any technology, responsible development and deployment are essential, given the potential societal and environmental impacts.

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Commentary – 1

Wikipedia: “Synthetic biology (SynBio) is a multidisciplinary field of science that focuses on living systems and organisms, and it applies engineering principles to develop new biological parts, devices, and systems or to redesign existing systems 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. It includes designing and constructing biological modules, biological systems, and biological machines, or re-designing existing biological systems for useful purposes. Additionally, it is the branch of science that focuses on the new abilities of engineering into existing organisms to redesign them for useful purposes.”

Genome.gov: “Synthetic biology is a field of science that involves redesigning organisms for useful purposes by engineering them to have new abilities. Synthetic biology researchers and companies around the world are harnessing the power of nature to solve problems in medicine, manufacturing and agriculture… In some ways, synthetic biology is similar to another approach called “genome editing” because both involve changing an organism’s genetic code; however, some people draw a distinction between these two approaches based on how that change is made. In synthetic biology, scientists typically stitch together long stretches of DNA and insert them into an organism’s genome. These synthesized pieces of DNA could be genes that are found in other organisms or they could be entirely novel. In genome editing, scientists typically use tools to make smaller changes to the organism’s own DNA. Genome editing tools can also be used to delete or add small stretches of DNA in the genome.”

Bio.org: “Synthetic biology is a new interdisciplinary area that involves the application of engineering principles to biology. It aims at the (re-)design and fabrication of biological components and systems that do not already exist in the natural world. Synthetic biology combines chemical synthesis of DNA with growing knowledge of genomics to enable researchers to quickly manufacture catalogued DNA sequences and assemble them into new genomes. Improvements in the speed and cost of DNA synthesis are enabling scientists to design and synthesize modified bacterial chromosomes that can be used in the production of advanced biofuels, bio-products, renewable chemicals, bio-based specialty chemicals (pharmaceutical intermediates, fine chemicals, food ingredients), and in the health care sector as well. Synthetic biologists are working to develop: standardized biological parts — identify and catalog standardized genomic parts that can be used (and synthesized quickly) to build novel biological systems; applied protein design — re-design existing biological parts and expand the set of natural protein functions for new processes; natural product synthesis — engineer microbes to produce all of the necessary enzymes and biological functions to perform complex multistep production of natural products; and synthetic genomics — design and construct a ‘simple’ genome for a natural bacterium.”

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Commentary – 2

Mustafa Suleyman: “Living systems self-assemble and self-heal; they’re energy-harnessing architectures that can replicate, survive, and flourish in a vast range of environments, all at a breathtaking level of sophistication, atomic precision, and information processing. Just as everything from the steam engine to the microprocessor was driven by an intense dialogue between physics and engineering, so the coming decades will be defined by a convergence of biology and engineering. Like AI, synthetic biology is on a sharp trajectory of falling costs and rising capabilities. At the center of this wave sits the realization that DNA is information, a biologically evolved encoding and storage system. Over recent decades we have come to understand enough about this information transmission system that we can now intervene to alter its encoding and direct its course. As a result, food, medicine, materials, manufacturing processes, and consumer goods will all be transformed and reimagined. So will humans themselves… Welcome to the age of biomachines and biocomputers, where strands of DNA perform calculations and artificial cells are put to work. Where machines come alive. Welcome to the age of synthetic life.”

Ted Anton: “There is nothing new about modifying life to make products that humans need…What is new is the speed, scale, and power of researchers’ ability to remake life. Today, hundreds of labs are fine-tuning gene pathways and DNA, and gene editing is taking place in homes, garages, and backwoods stables for cattle and horses. In agriculture, many of the tomatoes, apples, and oranges we eat are engineered to resist disease or to enhance their flavor or shelf life. Most cheese and many cold water detergents are made using enzymes produced by modified organisms. The same holds for many vegetarian meats. Some of the more whimsical quests seem drawn from the pages of science fiction—glowing trees to light highways, designer plants to cool Earth, and cells to detect and attack disease… Metabolic engineering, standardized parts, gene editing, directed evolution, and new forms of genetic material—and their applications in medicine, the environment, clothing, food, housing, biofuels, defense, remediation, and biomining—promise a better future… Engineered biology will be part of a matrix of processes to create a more sustainable world. It offers a possibility of realigning the human relationship with Earth. Call it a production platform and a portal to a new society that manufactured in partnership with nature, not in opposition to or domination of it. The creation of new life forms could enhance the world for the improvement of human beings.”

Matthew Bennet [via Masha Savelieff]: “There are so many exciting applications. In the short-term these include medical applications, such as CRISPR-based gene editing, bacterial therapeutics and biomaterials (i.e., cells embedded in materials to provide novel functions). In the long-term, I hate to even speculate…As our ability to engineer biology increases, the number of possibilities explodes. I believe that the killer application for synthetic biology has not been envisioned yet. Just as the first computer scientists probably never could have predicted smartphones, streaming devices and AI, I don’t think we can predict what our work will eventually become. But it will be amazing, of that I have no doubt.”

WSJ: “The rise of the cloud and distributed computing have boosted that effort, allowing for the processing of larger data sets. Scientists can perform genetic and DNA sequencing at a more rapid pace and scale, according to Jennifer Lum, co-founder of Biospring Partners. With a better understanding of the DNA composition and functions of cells of specific types, scientists can manipulate and redesign those cells to drive a particular outcome, from biofuels to disease-resistant plants. “It is collapsing time and expanding the aperture by which we are able to run experiments on a broader set of designs that scientists want to test on,” she said, describing the impact of those factors, while cautioning that plenty of challenges must still be solved.  A recent wave of discoveries has been made possible because of the availability of more computing power. Scientists can now better model and study the interactions of proteins, which are encoded by DNA sequences, Lum said.”

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In an article celebrating 20 years of the Human Genome Project, The Economist wrote: “Genomics has…come to form a framework for biology in the way that the periodic table forms one for chemistry. It touches everything. And with that, the ambitions for their subject of those biological prophets of the 1980s are being fulfilled in a manner they could scarcely have dreamed of.”

I love science fiction. Through the years, as I watched movies like Star Wars and Jurassic Park, and recent series like “The Expanse” and “Foundation”, I always thought of these as stories set very far in the future. Now, with the speed of innovation we are seeing in areas like AI and synthetic biology, I am not so sure. Perhaps, a few of the stories we have watched could come true in our lifetime. We are living through not just one revolution, but many simultaneous revolutions across disciplines, each building on the other.