The Burgeoning Impact of Synthetic Biology

By Lim Cheng Kai, Ning Mao and Lee Hui Ling

 

Biology has traditionally been thought of as a discipline whose applications are restricted to medicine or ecology. When one thinks of ‘doing biology’, it is usually associated with curing a disease or learning about the natural world. Yet, the world is changing significantly. Biology is now ‘eating the world’, as famed investment firm Andreessen Horowitz has espoused. It is worming its way into almost all industries we know, and this is most evident with the advent of synthetic biology.

 

What is synthetic biology? Simply put, it is the engineering of biology to conduct processes in a predictable manner – similar to all other engineering disciplines. What differentiates biology is that it involves the most complex systems. Evolution has gifted us with millions of years of complex molecular machinery and we have only begun to scratch the surface of its immense potential. More than just increasing knowledge, the interdisciplinary nature of synthetic biology propels applications–from designing microbes for the production of valuable chemicals to utilizing DNA as a computing material. The broad goals and concepts of synthetic biology hold great promise to transform industries as we know it.

More than just increasing knowledge, the interdisciplinary nature of synthetic biology propels applications–from designing microbes for the production of valuable chemicals to utilizing DNA as a computing material. The broad goals and concepts of synthetic biology hold great promise to transform industries as we know it.

 

In its previous incarnation as genetic engineering, synthetic biology was largely constrained to the alteration of existing organisms. While this is still a key part of synthetic biology, the field has greatly expanded its goals by taking new lenses to understand biology. Modifying organisms is no longer sufficient. Rather, it is the alteration, recomposition, and even synthesis of completely new biological parts that have become the aim of many synthetic biologists. The deeper understanding of the molecular architecture of life – how information in DNA is translated to proteins and how these proteins assemble to perform the many functions we see around us – underpins these advances. Similar to how progress in  various areas of engineering have changed our world completely by building up complexity from standardized parts, synthetic biology aims to develop and assemble those very parts – just that they happen to be carbon-based instead of silicon.

 

A key part of engineering involves simulations and model-testing. No engineer in today’s world would release a product without having first simulated its behavior in silico. Similarly, another goal in synthetic biology is the development of computational tools to accurately predict cellular behavior with every iteration of modification. Engineering biology requires predictability and reproducibility, and the community of today has embraced the capabilities of big data and computational power to simulate the cell. Companies such as Asimov and enEvolv have built their game-changing technology upon these platforms.

 

Even though the term synthetic biology has only begun to enter the scientific lexicon, it has sent waves across the biotech industry. A key concept synthetic biologyis the development of tools and platforms  that have the potential to be the basis of multiple applications. For example, a significant advancement in the synthetic biology arena was the discovery of CRISPR, which opened up multiple advances in gene editing for therapeutic uses and beyond. Another key area of progress is in the field of DNA synthesis, where companies such as Twist Biosciences have made breakthroughs in producing cheap and abundant DNA to assist in the construction of new genetic circuits.

 

The impact of synthetic biology can best be illustrated with examples. One key breakthrough in recent years is the engineering of yeast to produce artemisinin, an important antimalarial agent that was previously only found in plants. Being able to produce this compound in bioreactors on a larger scale will vastly increase the throughput and scale of the drug, making it more affordable to people affected by malaria. Another prominent example now is that of developing vaccinations and treatments for the Covid-19 virus. Synthetic biology companies are at the heart of this movement, with companies such as Moderna Therapeutics being the frontline candidates for developing novel vaccination candidates via their unique RNA platform technology. Such advancements showcase the increasing impact that synthetic biology has, and will continue to have, on our daily lives.

 

Due to the immense potential that synthetic biology has for disrupting old industrial processes and creating entirely new industries, this burgeoning field has exploded in investment popularity, with significant resources being put behind the field in the past few years. Funding has come from many places, ranging from traditional pharma and biotech to venture capital firms that used to deal with technology but are now transitioning towards what they see as the future. This increased investment, to the tune of USD12 billion in the last decade, with USD 4 billion coming from 2018 alone, showcases the immense growth the industry is experiencing. Valuations among companies are steadily increasing – a pioneering synthetic biology company, Ginkgo Bioworks, which engineers various cells and organisms for novel functions such as enabling nitrogen fixation in plant crops. The company recently attained a valuation of USD 4 billion. Andreessen Horowitz, a powerhouse in the tech investment scene which invested in Facebook, Airbnb, Instagram and Slack among others, has recently declared synthetic biology a significant area of investment which they are dedicating an entire arm of the company to. Similarly, Y-Combinator, arguably the startup accelerator, has started focusing on bio-based companies and synthetic biology startups as part of their programme.

 

The major pioneers in synthetic biology have come primarily from the usual scientific powerhouses such as the US, the UK, and China. However, the inherent applicability of it in industrial uses, coupled with the increasingly cheaper and easier methods to  engineer biology, has led to growth beyond these traditional stalwarts. In particular, Singapore has invested heavily into synthetic biology, with over USD19 million dedicated to funding synthetic biology research in the government’s RIE2020 plan. The pioneering institutes in Singapore consist of two major research hubs–the Biotransformation Innovation Platform at A*STAR, as well as the Synthetic Biology for Clinical & Technological Innovation (SynCTI) programme at the National University of Singapore (NUS). SynCTI is home to the Singapore Biofoundry, an integrated facility for streamlining the “Design – Build – Test – Learn” cycle fundamental to synthetic biology by using state-of-the-art automation. It is a cofounder of the newly established Global Biofoundry Alliance, a global initiative to drive the world towards a sustainable bioeconomy. Synthetic biology research in Singapore has largely focused on translational outcomes, with an emphasis on creating valuable chemicals and medical applications, along with novel food and nutrient production methods. With the increasing emphasis on food security in the future, the usage of synthetic biology to augment our food supply such as through engineering hardier crops or growing meat in labs have been heavily supported. To fuel the development of such research and facilitate the translational aspects of the work, industrial support via partnerships with major companies such as Wilmar International and Illumina have been set up. Such industrial collaborations allow for speedier transition from the lab to the real world. The Singapore Consortium for Synthetic Biology (SINERGY) has also been established to further strengthen the ties between academia and industry, enabling the transition of laboratory research from bench to market.

The Biofoundry at SynCTI whereby automation and high-throughput technologies enable the engineering of biology. (Image credit: SynCTI)

To further facilitate the growth of the synthetic biology industry, there has to be a significant talent pool in the population that is eager to take the leap into the field. Synthetic biology has embraced the ‘Maker’ ideology prevalent in many engineering fields, fostering the DIYBio movement – it has never been easier to get into engineering biology due to the advancements made in gene synthesis and editing. This movement is perhaps best exemplified by the International Genetically Engineered Machine (iGEM) competition. In essence, it is a global student competition which involves a months-long hackathon based on synthetic biology principles. The competition has had a significant impact in spreading the growth of synthetic biology amongst high school and tertiary institutes, with over 300 teams worldwide participating in its last iteration. Similar to a hackathon, there have been successful companies founded by participants of the competition – of which, Ginkgo Bioworks, synthetic biology’s unicorn, is a prominent example. Singapore also has a thriving student synthetic biology community due to this competition, with teams from the major tertiary institutes competing in previous iterations and consistently achieving top honors.

 

Synthetic biology has great potential in achieving change worldwide. Due to initiatives such as iGEM generating a talent pool ready to build this field, coupled with investments from governments and industries, Singapore is well-poised to be a major synthetic biology player in the region. The APAC region has contributed significantly to the iGEM competition, with a majority of participants coming from it. This, coupled with the increasing ease in which synthetic biology can be conducted, bodes well for the future of the industry in APAC and Singapore. We foresee that these developments will prove to be the first shoots of what will likely be a high-growth rainforest in the years to come.