The Genesis Machine

| INTRODUCTION |

SHOULD LIFE BE A GAME OF CHANCE?

Amy—The first time I felt the sharp twinge in my belly was during an important client meeting. Seated around the table were senior executives from a multinational information-technology company. We were developing the company’s long-term strategy when the twinge hit me again. I quickly handed the meeting off to one of my colleagues and ran to the bathroom. By then, a layer of sticky, dark blood had soaked through my black tights and adhered to my inner thighs. I couldn’t breathe. I couldn’t physically take in air. I slumped over on the toilet and finally allowed myself to sob, silently, so no one could hear.

I’d been eight weeks along. I was scheduled the following week for an early ultrasound. I’d already started thinking of names: Zev if the baby was a boy, Sacha if she was a girl. As I cleaned up the blood on my legs and the floor, I searched for answers, but kept arriving at the same place of anger and self-blame. It was my fault. I must have done something wrong.

The third time I felt that twinge, I already knew what to expect: blood loss and a humiliating trip to the drugstore for extra-large pads, followed by deep depression, insomnia, and a stream of questions with no answers. My husband and I saw the best fertility specialists in Manhattan and Baltimore, and we subjected ourselves to every test offered: blood tests to evaluate my hormones, tests to make sure I had enough eggs in reserve, and tests to determine whether I had any benign growths or cysts that might be causing problems. These were high-tech guesstimates, not answers.

We kept trying, and in a subsequent pregnancy I made it past the four-month mark, a milestone, and we finally allowed ourselves to feel excited. We arrived at the OB-GYN for a routine checkup. I was at eighteen weeks now, and my belly was starting to protrude. I laid on the exam table, and a technician squirted cold jelly onto my midsection, smearing it around with a sonogram wand. She punched a few keys on her keyboard, zooming in on a grainy, mostly black video. She apologized, mumbled something about her old equipment, and left the exam room, returning with another machine and my doctor. Again, she squirted cold jelly onto me, and again smeared it around, clicking her keyboard to zoom in as she glanced at my doctor, and then, reluctantly, back at me.

I don’t remember exactly what they said, but I remember my doctor taking my hand and the sound of my husband crying. I would be admitted for surgery to remove the fetal tissue. In the end, I was told that nothing was medically wrong with either of us. We were in our early thirties. We were healthy. We could get pregnant. The problem seemed to be my ability to stay that way.

One in six women will miscarry during her lifetime, and there isn’t a singular reason. Most often, the cause is a chromosomal abnormality—something goes haywire as the embryo divides—that has nothing to do with the health or age of the parents. It wasn’t my fault, I was told. My body just wasn’t cooperating.1

Andrew—Since age ten, I had been resolute in my intention to never have children of my own. We’d lived on a rural farm property on the outskirts of Montreal. My parents struggled with each other, and as a result, with me and my two siblings. The three of us had been born in quick succession: my brother was a year younger than me, my sister a year older. When my parents told us they were separating, I wasn’t upset, but I do remember thinking that my mom would have been happier as a nun. Instead, she became a single mother and a nurse working the night shift.

She slept during the day while we were at school. It helped that we were all independent, capable kids. I often escaped to the library—my second home, where I lived in the stacks. I’d bring home armfuls of books and see her off to work at 10 p.m., and I would keep watch over my siblings, often reading to them until dawn, when my mom returned home. Stories about traditional nuclear families felt foreign to me. I couldn’t relate. What made sense was the dependable logic of engineering, the wonders of biology, and the visions of science fiction. Sometimes, when my brother and sister drifted off to sleep, I stayed awake reading and thinking about life: where creatures both enormous and microscopic came from, how they evolved, and the promise of what they might become.

By the time I was eighteen, I wanted to study the fundamentals of life—genetics, cell biology, microbiology—but I had no intention of making children of my own. At that point, I was writing software and databases, thinking in both genetic and computer code, and I had a lifetime of research ahead of me. Sex was compelling, kids were not. The only forms of male birth control were mechanical, not medical, and they were hardly reliable. The guaranteed solution was vasectomy, so I sought out my doctor and asked for one. At first, he protested—at age eighteen, I was barely an adult, and certainly in no position to make such a drastic choice. Vasectomies were reversible, I countered, and I could bank sperm if I had doubts, but I didn’t. My conviction won his approval and referrals to urologists, but it would ultimately take six years to turn off the taps. Most of the specialists thought I was being rash and immature. I argued that I was just trying to be responsible. Still, once I got the vasectomy, there was no guarantee I’d be able to have children in the future.

Thirty years later, I connected with a beautiful woman at a conference who lit up when I talked about cells and who indulged my long-winded diatribes on DNA as software. Lying next to her one morning in her Manhattan apartment, I was overcome with a terrifying new feeling: I wanted children. I wanted that family, with her by my side. But I was now in my late forties, and I knew exactly what to expect medically and biologically.

When we decided to get pregnant, we were both hopeful, but realistic. On the day of my reversal, I fixed my eyes on the ceiling as the attendants pushed me into a surgical suite. The lights blurred past in a rhythmic pattern, and with each burst of light I cycled back to the doctor’s warning so long ago, and thought about how life paths can suddenly change. The tubes connecting my testicles to my urethra, which would have enabled sperm to leave my body, hadn’t been clamped or tied off—making a reversal easy. Instead, the surgeon had severed them entirely and cauterized them to make sure I didn’t leak internally. It would take a delicate microsurgery and general anesthesia to reconnect them.

We tried, and failed, to get pregnant for eighteen months. I knew what was wrong—and how little I could do now to change things. The surgery had been successful, but my body’s system had been shuttered for too long. Mechanically, there was nothing wrong with me. My body just wasn’t cooperating.

Right now, scientists are rewriting the rules of our reality. The anguish we both experienced as we struggled to become parents could be an anomaly in the coming decades. An emerging field of science promises to reveal how life is created and how it can be re-created, for many varied purposes: to help us heal without prescription medications, grow meat without harvesting animals, and engineer our families when nature fails us. That field, which is called synthetic biology, has a singular goal: to gain access to cells in order to write new—and possibly better—biological code.

In the twentieth century, biologists focused on taking things apart (tissues, cells, proteins) to learn how they functioned. This century, a new breed of scientists is instead attempting to construct new materials out of life’s building blocks, and many others are already achieving successes in the nascent field of synthetic biology. Engineers are designing new computer systems for biology, and startups are selling printers capable of turning computer code into living organisms. Network architects are using DNA as hard drives. Researchers are growing body-on-a-chip systems: picture a translucent domino embedded with nanoscale human organs that live and grow outside a human body. Together, biologists, engineers, computer scientists, and many others have forged a genesis machine: a complex apparatus of people, research labs, computer systems, government agencies, and businesses that are creating new interpretations, as well as new forms, of life.

The genesis machine will power humanity’s great transformation—which is already underway. Soon, life will no longer be a game of chance, but the result of design, selection, and choice. The genesis machine will determine how we conceive and how we define family, how we identify disease and treat aging, where we make our homes, and how we nourish ourselves. It will play a critical role in managing our climate emergency, and eventually, our long-term survival as a species.

The genesis machine incorporates many different biotechnologies, all of which were created to edit and redesign life. A series of new biological technologies and techniques, which broadly fall under synthetic biology’s umbrella, will allow us not just to read and edit DNA code but to write it. Which means that soon, we will program living, biological structures as though they were tiny computers.

It’s been possible to edit DNA code since the early 2010s using one of those technologies: CRISPR-Cas9.2 Scientists refer to a pair of “molecular scissors” to describe the technique, because it uses biological processes to cut and paste genetic information. CRISPR routinely makes headlines about groundbreaking medical interventions, such as editing the genes of blind people to help them see again. Scientists have been using CRISPR’s physical molecular scissor technique and splicing the DNA molecule back together in a sort of biological collage with letters rearranged into new places. The problem is that researchers can’t directly see the changes being made to the molecule they’re working on. Each move requires laboratory manipulations that must then be experimentally validated, making it all 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—making edits 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 akin to a 3D printer. The technology for DNA synthesis (transforming digital genetic code to molecular DNA) has been improving exponentially. Today’s technologies routinely print out DNA chains several thousand base pairs long that can be assembled to create new metabolic pathways for a cell, or even a cell’s complete genome. We can now program biological systems like we program computers.

These scientific innovations have fueled the recent and rapid growth of a synthetic biology industry intent on making high-value applications that include biomaterials, fuels and specialty chemicals, drugs, vaccines, and even engineered cells that function as microscale robotic machines. Progress in artificial intelligence has provided a significant boost to the field, as the better AI becomes, the more biological applications can be tested and realized. As software design tools become more powerful and DNA print and assembly technologies advance, developers will be able to work on more and more complex biological creations. One important example: we will soon be able to write any virus genome from scratch. That may seem like a frightening prospect, given that the coronavirus known as SARS-CoV-2, which causes COVID-19, has, as of this writing, resulted in the deaths of more than 4.2 million people worldwide.3

What makes viruses like SARS-CoV-2—and SARS, H1N1, Ebola, and HIV before it—so difficult to contain is that they are powerful microscopic code that thrive and reproduce with an unprotected host. You can think of a virus as a USB stick you’d load into your computer. A virus acts like a USB by attaching itself to a cell and loading new code. And as bizarre as this might sound at a time when we’re living through a global pandemic, viruses could also be our hope for a better future.

Imagine a synthetic biology app store where you could download and add new capabilities into any cell, microbe, plant, or animal. Researchers in the United Kingdom synthesized and programmed the first Escherichia coli genome from the ground up in 2019.4 Next, the gigabase-scale genomes of multicellular organisms—plants, animals, and our own genome—will be synthesized. We will someday have a technological foundation to cure any genetic disease in humankind, and in the process we will spark a Cambrian explosion of engineered plants and animals for uses that are hard to conceive of today, but will meet the global challenges we face in feeding, clothing, housing, and caring for billions of humans.

Life is becoming programmable, and synthetic biology makes a bold promise to improve human existence. Our purpose in this book is to help you think through the challenges and opportunities on the horizon. Within the next decade, we will need to make important decisions: whether to program novel viruses to fight diseases, what genetic privacy will look like, who will “own” living organisms, how companies should earn revenue from engineered cells, and how to contain a synthetic organism in a lab. What choices would you make if you could reprogram your body? Would you agonize over whether—or how—to edit your future children? Would you consent to eating GMOs (genetically modified organisms) if it reduced climate change? We’ve become adept at using natural resources and chemical processes to support our species. Now we have a chance to write 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’re on the cusp of a breathtaking new industrial evolution.

The conversations we’re having today about artificial intelligence—misplaced fear and optimism, irrational excitement about market potential, statements of willful ignorance from our elected officials—will mirror the conversations we will soon be having about synthetic biology, a field that is receiving increased investment because of the novel coronavirus. As a result, breakthroughs in mRNA vaccines, home diagnostic testing, and antiviral drug development are accelerating. Now is the time to advance the conversation to the level of public consciousness. We simply do not have the luxury of time to wait any longer.

The promise of this book is simple and straightforward: if we can develop our thinking and strategy on synthetic biology today, we will be closer to solutions for 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 we engineer and send into battle. If we wait to take action, the future of synthetic biology could be determined by fights over intellectual property and national security, and by protracted lawsuits and trade wars. We need to ensure that advances in genetics will help humanity, not irrevocably harm it.

The code for our futures is being written today. Recognizing that code, and deciphering its meaning, is where humanity’s new origin story begins.

This is a book about life: how it originates, how it is encoded, and the tools that will soon allow us to control our genetic destinies. It is also about the right to make decisions about life, defined for a new generation along scientific—as well as ethical, moral, and religious—terms. With powerful systems in place, to whom will we grant the authority to program life, to create new life forms, and even to bring former life forms back from extinction? Answering these questions will force humanity to resolve economic, geopolitical, and social tensions.

This book is also about you and your life, and the decisions you will need to make in your lifetime. We are standing on the precipice of sweeping change, and you must play an active role in your own future by making informed decisions today. You will need to make choices that have consequences, such as whether to have your own genome sequenced and what to do with that data. Or, if you are planning to become a parent, whether to freeze your eggs, pursue assistive reproductive technology such as in vitro fertilization (IVF), or use genetic screening to select the strongest of your embryos. These are decisions with which we are intimately familiar. In fact, they are what compelled us to write this book.

In order to see what future the genesis machine might someday build, it’s important to revisit the past. In the first part of this book, we’ll explain synthetic biology’s origin and the history of how researchers decoded life—and eventually manipulated it—with the intent to create synthetic organisms whose parents were computers. In Part Two, we will reveal the new bioeconomy created by the genesis machine, which includes the myriad, fantastical medicines, foods, coatings, fabrics, and even beers and wines that entrepreneurs are attempting to make—as well as the possible biotechnology solutions to solve problems such as the spread of ocean plastics, the increase in extreme weather events, and the ongoing possibility of dangerous viruses that could lead to new pandemics. We’ll also address the risks that synthetic biology poses, which range from cyber-biology hacking to the looming genetic divide, pitting wealthy engineered people against those who will not be able to afford technology-assisted reproduction. In Part Three we’ll explore different futures in the form of creative, speculative scenarios suggesting the many ways in which the genesis machine might transform the world. Finally, in Part Four we offer our recommendations for ensuring that the genesis machine gives birth to the best of these possible futures.

But first, you should meet a young man named Bill.

| ONE |

SAYING NO TO BAD GENES

The Birth of the Genesis Machine

The long days had shortened and cooler nights hinted at autumn in Duxbury, Massachusetts, a pretty seaside town just south of Boston. Bill McBain was a gifted student with wide-ranging interests in photography, math, and journalism, but in other ways he was unremarkable: on the first day of eighth grade, it was obvious that Bill had gone through a growth spurt over the summer, just like his friends. He was now four inches taller. But unlike the other kids, he’d also lost weight. While his male friends were starting to fill out and put on some adolescent muscle, Bill was spindly—all elbows, ribs, and knees.

Bill went to bed early every night and woke up exhausted every morning. He started drinking water—lots of it—but couldn’t seem to ever quench his thirst. It was 1999, and transparent plastic Nalgene water bottles—intended for rugged outdoor use—were suddenly wildly popular as a fashion accessory at school. But for Bill, his Nalgene was a necessity: he filled it with water between classes and guzzled from it continuously. Once, while staring at the ounces marked on one side of the bottle, Bill—who loved math—drifted off, making some mental calculations. He estimated that he was drinking four gallons of water a day, sometimes five.

In February, a family friend visiting for the afternoon watched nervously as Bill gulped from his water bottle again and again. As a nurse, she immediately recognized the warning signs and made a quick, discreet trip to the bathroom to confirm her hunch: indeed, the toilet seat was sticky to the touch, and when she bent over to take a whiff it was sickly sweet. She asked Bill’s parents to take him to the clinic to get his blood tested the next morning.

On the way there, the family pulled over for a quick breakfast, and Bill ordered a cinnamon sugar bagel along with a large red Gatorade to wash it down. It wasn’t the best meal to eat before a fasting blood sugar test, but he didn’t know any better. At the clinic, the doctor pricked Bill’s finger with a tiny needle and squeezed a droplet of blood onto a test strip attached to a meter. Within a few seconds the meter beeped, and the screen flashed “high.” This meant that his blood sugar level had spiked above 500 milligrams per deciliter (mg/dL). The fasting blood sugar of someone with a normal pancreas would typically fall between 70 and 99 mg/dL, or just below one-thousandth of a gram per one-tenth of a liter. In other words, barely noticeable, because a healthy person’s system quickly breaks down sugar and converts it into energy, so there isn’t much left in the bloodstream. If a healthy person takes that same blood test right after eating, the number will be higher for a few hours, as their body processes the food, but it will still be less than 140 mg/dL.

The doctor drew more blood and sent it to his lab for a detailed analysis. The results left him at a loss for words. Back in his office with Bill and his parents, he sat down. He looked from his file folder to Bill and his parents, and then back to his folder again. Bill’s blood sugar reading was a staggering 1,380 mg/dL. His sodium, magnesium, and zinc levels were so far off the charts that the pH of his blood had actually changed. He was on the verge of sinking into a diabetic coma, if not worse: blood like that could kill.