Configuration machine: programming live cells like microcomputers

The following is an excerpt from The Gene Machine: Our Quest to Rewrite Life in the Age of Synthetic Biology by Amy Webb and Andrew Hessel. Copyright © 2022. Available from PublicAffairs, an imprint of Hachette Book Group, Inc.

The Genesis Machine incorporates many different biotechnologies, all created to modify and re-engineer life. A series of new biological technologies and techniques, broadly falling under the umbrella of synthetic biology, will allow us not only to read and edit the DNA code but to write it. Which means we will soon be programming living biological structures as if they were small computers.

It has been possible to modify the DNA code since the early 2010s using one of those techniques: CRISPR-Cas9. Scientists refer to a pair of “molecular scissors” to describe the technique, as it uses biological processes to cut and paste genetic information. CRISPR technology routinely makes headlines about pioneering medical interventions, such as modifying the genes of blind people to help them see again. The scientists used CRISPR’s physical molecular scissors technology and stitched the DNA molecule back together again in a kind of biological collage with the letters rearranging in new places. The problem is that researchers can’t directly see what changes are being made to the molecule they’re working on. Each step requires lab treatments that must be empirically validated, which makes them very indirect, labor intensive, and time-consuming.

Synthetic biology digitizes the manipulation process. DNA sequences are loaded into software tools – imagine a text editor for DNA code – which makes modifications as simple as using a word processor. After the DNA is written or edited to the researcher’s satisfaction, a new DNA molecule is printed from scratch using something similar to a 3D printer. The technology of DNA synthesis (the conversion of digital genetic code into molecular DNA) has greatly improved. Today’s technologies routinely print DNA sequences several thousand base pairs long that can be assembled to create new cell metabolic pathways, or even the entire cell genome. We can now program biological systems like computer programs. These scientific innovations have fueled the modern and rapid growth of the synthetic biology industry that aims to create high-value applications that include biomaterials, fuels, specialty chemicals, pharmaceuticals, vaccines, and even engineered cells that function as small-scale robotic machines. Advances in artificial intelligence have provided a huge boost to this field, as the better artificial intelligence becomes, the more biological applications can be tested and realized. As software design tools become more powerful and DNA printing and assembly techniques develop, developers will be able to work on more and more complex biological innovations. One interesting example: we will soon be able to write any virus genome from scratch. This might seem like a frightening prospect, given that the coronavirus known as SARS-CoV-2, which causes COVID-19, has as of this writing killed more than 4.2 million people worldwide.

What makes viruses like SARS-CoV-2 — and SARS, H1N1, Ebola, and HIV before them — so difficult to contain is that they are a powerful microscopic code that thrives and reproduces with an unprotected host. You can think of a virus as a USB drive that gets mounted into your computer. A virus acts like a USB by attaching itself to a cell and uploading new code. And while this may sound strange at a time when we live in the shadow of a global pandemic, viruses may also be our hope for a better future.

Imagine a synthetic biology app store where you can download and add new capabilities to any cell, microbe, plant or animal. UK researchers synthesized and programmed the first Escherichia coli Genomes from the ground up in 2019. Next, gigabase-scale genomes of multicellular organisms – plants, animals and our own genomes will be synthesized. We will one day have a technical basis for treating any genetic disease in the human race, and in the process we will spark a Cambrian explosion of plants and animals engineered for uses that are hard to imagine today, but which will meet the global challenges we face in feeding, clothing, housing, and caring for billions of people.

Life is becoming programmable, and synthetic biology offers a bold promise to improve human existence. Our goal in this book is to help you think about the challenges and opportunities that lie ahead. Within the next decade, we will need to make important decisions: whether to program new viruses to fight disease, what genetic specificity will look like, who will “own” organisms, how companies should earn a revenue from engineered cells, and how to contain a synthetic organism in the laboratory. What choices would you make if you could reprogram your body? Do you agonize over – or how – to adjust your children in the future? Would you agree to eat GMOs (genetically modified organisms) if you reduce climate change? We have become adept at using natural resources and chemical processes to support our species. Now we have a chance to write a new code based on the same architecture as all life on our planet. The promise of synthetic biology is a future built by the most powerful sustainable manufacturing platform humanity has ever had. We are on the cusp of an astonishing new industrial development.

The conversations we’re having today about AI — misplaced fear and optimism, irrational excitement about market potential, statements of willful ignorance from elected officials — will mirror the conversations we’ll soon have about synthetic biology, an area receiving more investment due to the novel coronavirus. As a result, breakthroughs in mRNA vaccines, home diagnostic tests and the development of antiviral drugs are accelerating. Now is the time to bring the conversation to the level of public awareness. We simply don’t have time to wait any longer.

The promise of this book is simple and straightforward: if we can advance our thinking and strategy on synthetic biology today, we will be closer to solutions to the immediate and long-term existential challenges posed by climate change, global food insecurity, and human longevity. We can prepare ourselves now to fight the next viral outbreak with a virus that we are engineering and send into battle. If we wait for action, the future of synthetic biology can be determined by battles over intellectual property and national security, protracted lawsuits and trade wars. We need to make sure that advances in genetics will help humanity, not irreversibly harm it. Our futures symbol is being written today. Realizing this symbol and deciphering its meaning, is where the story of the new origin of humanity begins.

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