Recently, our colleagues Drs. Anderson and Ross wrote about the “over the horizon” technologies that will reshape and improve the world in the coming years, including energy-related tech, commercial space, and the metaverse. Of those described, which one will be able to:
- Enhance the wellness of the global population?
- Improve crop production in a world of accelerating climate change?
- Replace petroleum as a manufacturing material?
- Allow nations to domestically manufacture critical medicines and materials?
- Remediate waste and decarbonize the atmosphere?
- Be powered by the one fusion reactor that actually works?
It’s biotechnology.
Biotechnology is critical to solving global issues from food security to environmental remediation to equitable healthcare. Why? Because of the astonishing power of biology to organize matter:
- with atomic precision,
- at planetary scale, and
- directly or indirectly powered by the sun.
Just how biology accomplishes this feat has been intensely studied since James Watson, Francis Crick, Rosalind Franklin, and Maurice Wilkins described the structure of DNA in 1953. This work is often cited as the beginning of the “biorevolution” because it opened the door to current understanding that this marvelous molecule contains the coded instructions that determine all biological structures and functions. Because life is programmable, understanding and using this code responsibly will ultimately be humanity’s greatest technological achievement.
The revolution rolls onward. Understanding the code, and learning to read it (DNA sequencing), write it (DNA synthesis), and edit it (using tools like CRISPR/Cas) is work that is ongoing all over the world and generating enormous amounts of both raw DNA sequence data and information on how that data works inside cells to produce useful functions and goods. In fact, there is so much DNA sequence and related data now that another technological revolution is being used to supercharge the biorevolution: the revolution in computation, including artificial intelligence and machine learning (AI/ML) and quantum computing. AI and ML (and soon, quantum) are being applied to large biological datasets to help manufacture existing biological products (like insulin) and to make products that don’t exist in nature (like new cancer treatments and industrial materials). When engineered biology, designed with AI and ML tools, is combined with the most advanced lab automation (to do more lab work faster), you get what is now called synthetic biology, or “synbio.”
Synbio is the use of biology, AI/ML, and lab automation to accelerate the engineering cycle of design-build-test-learn to make increasingly sophisticated and useful biotechnology products. To use a hockey analogy: using AI and ML on genomics data, you take better aim at the goal when making biology designs that are useful, and with lab automation, you take a lot more shots on goal.
Talkin’ ‘bout the generations. The pace of technological progress is breathtaking, no less in biotechnology than in any other field. In the last decade alone, we have seen advances in DNA sequencing, synthesis, editing, AI/ML, and lab automation that have driven down the cost of the design-build-test-learn cycle so fast that entrepreneurs have founded no fewer than three generations of synbio companies:
- Synbio 1.0: companies that developed “biofoundries” in which a variety of organisms could be engineered to make products specified by commercial partners, who brought both technical and economic requirements that needed to be built into solutions. Some examples include Ginkgo Bioworks* and Amyris.
- Synbio 2.0: companies founded with the intention of leveraging synbio 1.0 biofoundries to address specific industrial sectors: industrial chemicals, fibers, fuels, dyes, pharmaceuticals, novel foods, cosmetics, environmental remediation and waste recycling, and many others. Some examples include Bolt Threads and Impossible Foods.
Ginkgo Bioworks is the quintessential, foundational synbio 1.0 company. In collaboration with their customers, they engineer microorganisms to produce a wide variety of small molecule products, as well as assisting customers in improving the production of existing bio-made products. Moreso than any other biofoundry-centered synbio company, Ginkgo Bioworks’ influence in launching synbio as an industry has been immense. As the largest designer of synthetic DNA in the world, their foundries have supported synbio 2.0 companies in every synbio application sector and have even incubated and spun out synbio 2.0 companies themselves.
Note that synbio 1.0 and 2.0 companies target microorganisms when thinking about engineering. Why? Microorganisms are frankly smaller and simpler than organisms we can see, and so are their genomes. Much of biology research done in the last 70 years has focused on microbes because they were the training wheels, if you will, of molecular biology. Microorganisms will always be a cornerstone of biotechnology because of their tremendous capacity to make useful products; therefore, synbio 1.0 and 2.0 companies will not become obsolete, but more and more closely embedded in manufacturing generally.
But plants and animals also make products that are useful–what about them? They are larger and much more complex, and engineering them is, comparatively, really challenging. That leads us to:
- Synbio 3.0: companies that engineer complex organisms (like animals and plants) to modify correspondingly complex structures (tissues, organs, organ systems, plus the shapes and sizes of entire organisms). Companies pursuing these projects include Chi Botanic, Living Carbon, and Colossal*.
We know a lot about how bacteria live, eat, make useful products, and make more bacteria. We know much less about how a single plant or animal cell becomes an oak tree (instead of a maple) or a beagle (instead of a badger). Why the interest in a company like Colossal, which was founded with a mission to “de-extinct” the wooly mammoth and other species? Strategically, it’s less about the mammoths and more about the capability. The next wave of progress in synbio will lead to advances in our ability to shape both form and function in organisms at the macroscopic level. Solving the challenges that must be overcome in engineering animals and plants (making massively parallel and highly accurate genome edits, making healthy sperm and eggs from edited stem cells, and gestating large animals to term) will unlock such capabilities as programming the physical properties of wood to improve building materials, preventing the extinction of not-yet-extinct but endangered animal species, sequestering carbon from the atmosphere, further enhancing crop species to tolerate increasingly severe climatic changes, and curing human diseases such as sickle-cell anemia, beta thalassemia, Duchenne muscular dystrophy, and many kinds of cancer.
Why is this a big deal? We now sit at a pivotal point in history, where transnational issues (pandemics, climate change, population growth, human migration) intersect with nation-to-nation competition that will increase the potential for global conflict in coming decades, a reality that was formally recognized this week by the Biden administration in the release of the Executive Order (EO) on Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy. At a White House summit held to discuss the EO, participants made clear the importance of U.S. government support for synbio through early-stage funding of innovative companies and the training of world-class scientists and engineers. Nations whose biotechnology infrastructure and industry excel will be well-positioned to achieve early those goals listed at the top of this article. Perhaps more importantly, leadership in biotechnology will allow the U.S. to help set the ethical, as well as the technological, standards for the use of this technology. How we employ the potentially staggering power of biotechnology to shape the planet and humanity itself will matter as much as our ability to do so.
*Disclosure: IQT portfolio companies.