The coming Industrial Revolution

The third generation of synthetic biology companies are growing exponentially, Paul-Bunyan-like. In North America, companies are voraciously engineering their ecosystems.

By S Ramadorai, Raman Srinivasan & S Shivaramakrishna

Faced with commercial and technical headwinds, smart synbio companies evolved. “Synbio_as_a_Service” became the new business model. An insatiable demand for low-calorie sugar led to the processed foods industry seeking synthetic biology. Companies such as Evolva and Zymergen developed novel and sustainable pathways for advanced materials, and let enterprise customers partner in the scaling up. Evolva developed a scalable route to a superior sugar substitute normally found in minute quantities in stevia leaves.

Amyris also joined the zero-calorie sugar rush by developing similar substitutes. In fact, “sugar reduction platforms” are now a major competitive advantage in the global ingredients business. Changing consumer preferences and investments in zero-calorie alternatives made by synthetic biology have led to a 50% decline in global sugar prices in the last decade.

However, Indian farmers, given the incentives, cultivate more sugarcane. Satellite data shows that sugarcane cultivation depletes non-renewable water across the nation. Cheaper sugar also leads to larger disease burden. Yet, our addiction to sugarcane grows.

A century ago, Mahatma Gandhi launched the Champaran Satyagraha to help indigo farmers. German chemists had invented synthetic chemistry routes to develop indigo using aniline that could be scaled industrially. In less than 20 years, the demand for indigo grown in India had dropped almost to zero. History, it is said, does not repeat, but rhymes. Now, the rapid progress in synthetic biology has the ability to make obsolete many sectors of our rural economy.

Nature provides us with many examples of ecosystem engineers. Beavers in North America reshape their landscapes. They do this by felling down fir and pine trees to build dams across streams. The third generation of synthetic biology companies are growing exponentially, Paul-Bunyan-like. In North America, companies are voraciously engineering their ecosystems.

These companies—Ginkgo is one example—are creating synthetic biology operating systems and building out an ecosystem of partners and customers. Together, they are developing innumerable products for multiple markets. These next-generation companies are not just growing but partnering with the giants in the multi-trillion-dollar chemicals industry. Sumitomo Chemicals has launched a synbio hub in the USA.

Zymergen, a Sumitomo partner, has built a proprietary database of 75,000 bio-molecules derived from soil microbes alone. It calls this a “metagenomic database.” In order to imagine the power of such databases, it is worth recalling that just one soil microorganism powers a six billion dollar company today! A single teaspoon of soil can contain millions of different microbes. The genome of each microbe can be sequenced in a fast and cheap manner, out in the field, with a laptop and a small device that plugs in like a USB dongle. Thus, when one sequences the genome of a large number of different microbes in a given environment, it results in a meta-genomic database. Usually, the vast majority of these microbes have never been studied before.

Our ability to “read” nature in a quick and affordable manner out in the field has been powered by low-cost DNA sequencing technology, and solid-state spectroscopy. Using this data, it is now feasible to identify the genetic sequences responsible for the production of particular molecules in nature and then to reverse engineer the same in well-understood microbes that serve as biotech workhorses.

For example, a leading vegan hamburger company utilises Pichia pastoris to produce heme molecules that recreate the taste and aroma of animal blood without having to kill animals at all. Third-generation synbio companies are racing to assemble vast metagenomic databases to discover previously unknown biological pathways to various molecules.

Our ability to “read” nature also lets us see the convoluted paths nature has taken over millions of years of evolution. While looking at the data objectively, many biologists envision alternatives more efficient than natural evolution. Somewhat more conservatively, many third-generation synthetic biology start-ups are motivated by a desire to build more economical, and sustainable alternatives to a global economy powered by petrochemistry.

Almost everything around us is derived from petrochemicals: plastics, fertilisers, clothes, and even some food flavours. Our addiction to petrochemistry is leading to irreversible damage to the planet and all its denizens, including us humans. To some extent, this also explains the early emphasis on biofuels in the synthetic biology industry.

“The only way to improve people’s quality of life and reduce their impact on the environment is through biology,” says, Zach Serber, co-founder and Chief Science Officer of Zymergen. “Biofacturing is the answer.” Zymergen’s neologism, “biofacturing” is the application of synthetic biology to make both traditional materials as well as novel materials. Zymergen asserts that we are “just beginning to delve into nature’s vast molecular library to find biomolecules exquisitely suited to a new generation of products… at one-tenth the cost of traditional chemistry.”

When synbio companies like Zymergen succeed in embedding themselves deep in the complex global supply chains for advanced materials or ingredients, we will witness a new paradigm in manufacturing, with biology, and a new paradigm with deep implications for the health of our planet and for all its residents. Given that biology is indeed the most elegant and precise way of making (living) things, it is reasonable to expect that the new discipline of synthetic biology will lead us to a much-needed Industry 5.0.

Ramadorai is former vice-chairman, TCS, Srinivasan is head, TCS Ignite and Shivaramakrisha is researcher, TCS