Daniel Suarez on the future according to CRISPR

Synthetic biology is changing what it means to be human. For thousands of years, we’ve used technology to shape biology. We domesticated and bred plants and animals, trained our minds with meditation and asceticism, drove species to extinction, and ingested alcohol and narcotics to alter our own brain chemistry. More recently, we’ve upped the ante with modern pharmaceuticals, implants, medical devices, biofeedback training, and prosthetics.

But these myriad accomplishments pale in comparison to synbio.

Advances in computational biology and genetic editing techniques like CRISPR empower us to reassemble the building blocks of life. We are producing spider silk from yeast, designing drought-resistant plants to survive the privations of climate change, growing meat in petri dishes, editing cells in adult humans in an attempt to cure HPV, and embedding computer viruses in DNA. In his near-future thriller, Change Agent, Daniel Suarez prototypes the cascading consequences of this revolutionary technology.

Synbio shapes every aspect of Change Agent’s world. Agriculture has moved from fields to skyscrapers where bespoke crops generate unprecedented yields. Parents wring hands over whether and how to modify children that could all too easily end up on the losing end of an arms race for desirable traits. Cheaply manufactured designer drugs deliver the perfect high every time. Governments struggle to reform and enforce pertinent regulations and geopolitical power shifts to places with less stringent rules. Biotech corporations profit from the economic boom and strengthen a draconian intellectual property regime that privatizes ownership of life itself.

Change Agent is the future according to CRISPR, and the implications are staggering.

Synbio would never have been possible without the successive leaps and bounds that computing has made over the past few decades, and the information and biological technology revolutions have more in common than you might think. Like cloud computing, offsite sequencing labs have dramatically increased the pace and lowered the costs of research, empowering DIY biohackers alongside career scientists. Like the internet, synbio is not easily restricted by geographic borders or governance, democratizing tools of extraordinary power and raising the spectre of catastrophe. Like social media and online anonymity, genetic manipulation threatens traditional definitions of identity, forcing us to reevaluate what it means to be human.

Suarez riffs on these themes and more, making Change Agent a veritable cornucopia of speculative insights into the second and third order effects of synbio advances. Each detail shines with the warm glow of rigorous polishing. This is science fiction for scientists. Suarez did an enormous amount of research to inform the future he presents, reading countless books and scientific papers, interviewing experts, visiting cutting edge research facilities, and vetting his creations with leaders in the field.

The result is a pulse-pounding thriller in the vein of Michael Crichton. But even after you’ve finished the book and your adrenaline runs down, you’ll be left wondering whether, in our race to hack life and build the future, we are forgetting the moral of Prometheus’ ancient tale.

Suarez was kind enough answer a few questions about how synbio will shape our world, our most common misconceptions about it, where it will impact our personal and professional lives, and what it means for our social and political institutions. He also shares details on his inspirations, research, and creative process.

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While CRISPR makes headlines, the applications still feel limited to the lab, remote from our daily lives. But every aspect of the future Change Agent portrays has been revolutionized by this fascinating technology. Why did you choose to explore this particular scientific frontier? How will it shape our world over the coming decades?

I chose CRISPR because it's going to have a huge impact on the world and relatively soon. CRISPR may seem like it's limited to multi-million dollar university and corporate labs, but it's already possible to start genetically editing single-cell organisms at home.

In fact, CRISPR has helped a burgeoning open-source movement in synthetic biology (or 'synbio') that was originally championed by Harvard geneticist George Church.

I was first introduced to synbio a few years ago while on a visit to the MIT Media Lab. Several fascinating projects at MIT were aimed at 'programming' single-cell organisms like bacteria, yeast, and algae to do productive work—from manufacturing pharmaceuticals to biofuels. CRISPR gene-editing (developed in 2012) made creating these synthetic organisms easier. It was clear to me that synbio and CRISPR together were going to spark a revolution in open-source, DIY biotech.

I think the big successes in synbio will be created not by multi-billion dollar labs but by newcomers experimenting without preconceptions—in much the same way that early Internet entrepreneurs disrupted existing gatekeepers. In the context of biology that's both exhilarating and terrifying.

Knowing this, synbio and CRISPR became obvious fodder for a high-tech thriller.

What aspect of synbio is most misunderstood in the popular imagination? What do laypeople get wrong in cocktail conversations and armchair debates? What do experts get wrong when trying to communicate its real promise, risks, and import?

I think the first thing the public gets wrong on this topic is that synbio is decades away from impacting society. Take a drive through South San Francisco and you will find biotech startup after biotech startup, many of them focused on mining DNA data and/or generating DNA-based biotech innovations. CRISPR startups abound worldwide.

This isn't some distant future. It's starting now, and every month will bring news of CRISPR-related breakthroughs and new ethical dilemmas relating to humanity's increasing ability to manipulate DNA—the building blocks of all living things.

I wouldn't say the experts are getting things wrong. I think industry leaders like Dr. Jennifer Doudna, co-developer of CRISPR genetic editing, have been very responsible in their public pronouncements about the technology, cautioning entrepreneurs and policymakers to proceed with care and to not let the technology outpace our ability to cope with its social and ethical implications. Researchers have also enacted a voluntary moratorium on editing human embryos.

Will that work? It's worth a shot. What else can they do to restrain risky biotech research, especially across borders? There's no way to put this genie back in the bottle, and the very nature of CRISPR—its low cost and ease of use—will present challenges to those urging caution. Already in China we see CRISPR research underway focused on curing heritable genetic disorders in human embryos. The embryo edits conducted there, if successful, could be shifted from curing disorders to 'gifting' children with genes associated with longer life, stronger bones, faster muscles, or better memories. The long-term effects of such edits are unknown, but the only thing holding back the research at this point is prudent caution—not technical limitations.

And should an edit convey advantages to a child in one place, there will be a biotech race to see who can unlock the next major discovery. And big money will reward the first-movers—even if the ultimate consequences are not clear for a generation or two.

And it is here where I think experts could place more emphasis: Even if a genetic edit seems to convey advantages, that doesn't mean we fully comprehend the complexities involved. We could be editing ourselves into deep trouble.

As any new scientific discovery matures into technology and migrates from the hands of researchers into the world at large, our social and political institutions must evolve to deal with the changes it inevitably precipitates. What are the most important moral, social, and political questions raised by CRISPR and synbio? How do our institutions currently manage them? What new policy frameworks do we need to consider going forward?

One of the key challenges genetic editing and synthetic biology will present to society is whether it's immoral NOT to genetically modify plants, animals, and even humans as humanity contends with the consequences of anthropogenic climate change. I say this because there are long-established, well-organized constituencies on both sides of the GMO debate—corporate and university labs on one hand, and anti-GMO activists on the other. No matter which side you favor, the rationale for both is about to be disrupted.

I, myself, have long been opposed to most GMO's—but not because I thought genetic modification was inherently wrong. What I objected to about GMO's was that patented genetic sequences were being used as a form of intellectual property virus—proprietary DNA cross-pollinating with long-cultivated heirloom seed varieties and then being used as legal leverage to convince farmers to buy into proprietary agriculture 'systems', thus reducing genetic diversity and making food production MORE susceptible to a major disruption.

I also sympathized with the organic food movement because they want food to be the product of a healthy, sustainable, and diverse ecosystem. And let's face it: most people want that.

However, change is the only permanent state in the natural world, and so any effort to force food, animals, and even humanity to remain exactly as they are is doomed to failure—and even worse, if successful, will doom us.

So change is necessary. But what kind of change? In the natural world mutations favor fitness – a state constantly in flux due to the mutations of viruses, bacteria, parasites, predators, and the ever-changing state of our environment. That means there is no 'ideal' organism. There is only an organism best-suited-for-this-moment—and that moment will change.

The latest wild card, however, is anthropogenic climate change. Overwhelming evidence indicates the warming atmosphere stems from fossil fuel use and industrial farming (i.e. deforestation, agricultural run-off, etc.).

Environmental activists can legitimately claim that our warming atmosphere was caused by the same industrial processes to which they've long been opposed. However, as the climate shifts, food crops and animals dependent on specific ranges of temperature and rainfall are perishing. Extinctions are already occurring at 100 to 1,000 times historical rates in what's known as the 'Sixth Extinction' (I recommend Elizabeth Kolbert's 2014 non-fiction book of the same name by for those wanting to know more). At *current* rates 75% of all species on Earth could be extinct in just three human lifetimes.

What do we do about this? We try to mitigate climate change, of course. However, synbio and genetic editing might offer our only chance to preserve biodiversity by accelerating evolution to enable the environment to survive our mistakes, while we struggle to create a less polluting, more sustainable modern civilization. In other words, it buys us a little more time to get our act together.

You can see the obvious conflict: There's no guarantee that humanity will mend its polluting ways even if it does modify the genetics of key plants and animals to cope with a warmer, more unpredictable world. Likewise, there's no guarantee that our genetic edits will be capably done – and our track record for comprehending the complex interdependence of genes and creatures within an ecosystem is not good.

And yet, doing nothing is no option either. Animals, plants, and even humanity will not be able to evolve at a speed commensurate with the challenges of climate change. Going back to an 18th century agricultural system simply cannot feed the Earth's seven billion people—much less during times of drastic climate uncertainty.

This brings me back to the two sides in the current GMO debate that I mentioned earlier: corporate and university labs versus anti-GMO activists. Both of their traditional positions will become untenable within a decade.

In an age of low-cost, CRISPR genetic editing and DIY synbio-hacking, it will no longer require a multi-million dollar lab or highly skilled scientists to modify organisms. Even Internet-connected villages in the developing world will theoretically be able to obtain the tools and know-how to modify their traditional crops to withstand droughts, deluges, or new pests.

Corporate labs won't relish the open-source competition—but biology is the *original* open-source.

And who are we to say that people in the developing world must starve rather than modify their crops—especially if my industrialized society was the cause of their changing climate?

An open-source biology movement akin to the rapid spread of the internet presents huge risks and huge opportunities for everyone—not least because this time the code we'll be writing will be the code of life itself.

How will our social and political institutions cope with this level of rapid, fundamental change? Anyone with answers to that question will be much in demand.

The world of Change Agent is filled with technological marvels and nightmares, but one of the most interested parts of the novel is how this new reality challenges the characters to confront age-old philosophical questions about identity. When we can rewrite genes, what does that mean for our sense of self? When nature herself is malleable, how does she interact with nurture in forming who we become? How does synbio interact with persistent surveillance?

Human identity already struggles in the digital age (where people maintain multiple fictional identities in various web-based subcultures).

But I wanted to explore what would happen to our sense of self if literal, physical change at the DNA level was possible. In such a case, what does one generation derive from the previous one? What do children owe to parents? What fundamental assumptions of all human societies are blown to the wind as a result of the ability to rewrite our own genetics?

One possible result might be the final and permanent demise of racism. If everyone could revise their genetic sequence—even as mature people—then physical attributes would have no more weight in the real world than they do in the virtual ones. However, the exclusionary instincts of humanity might move on from phenotypical traits toward our underlying psychology—becoming prejudiced against modes of behavior.

In that sense, our quest to understand ourselves would hinge less upon our physical bodies and more upon our beliefs and actions. However, genetic edits to the human brain—especially those received in adulthood—might call into question the very idea of 'free will.' I suspect individuals in a society with rampant genetic editing will seek to record their DNA 'signature' so that any unintended edits can be quickly detected and reversed.

Control of one's genetic sequence will indeed become a source of legal and ethical debate. Will 'original' recipients of a genetic complement inherited 'naturally' have legal standing to defend against the use of their DNA by others? If artwork on the Internet is routinely lifted and claimed by others, think how much more alarming it would be to find your DNA lifted from a saliva or skin cell sample—and that your physical form is available for purchase in a genetic surgery catalog?

Needless to say, both police work and surveillance become infinitely more challenging in a world where people can transform indistinguishably into others. Fingerprints and DNA analysis wouldn't prove much. Neither would security camera footage.

Reading Change Agent, I was struck by how its core premise spirals into so many recursive thought experiments. In Michael Crichton’s Jurassic Park, the core “what if” question is limited to whether we could use gene-editing to resurrect dinosaurs. But in Change Agent, the core premise presents a scenario in which nothing remains unchanged or untouched by this Promethean innovation. What research did you do to inform the world you build in the novel? How did you go about generating and vetting ideas? What real world resources did you draw on to develop or strengthen your various theses?

Part of the inspiration for Change Agent came from reading early disquisitions on the ethical dilemmas relating to CRISPR-editing of human embryos—specifically the potential to create designer babies. That seemed like more of a background element to me. Society grappling with the natural urge of parents to 'better' their children through unnatural means is interesting, but the solution also seemed obvious: authorities and reputable scientists in such a near-future society would seek to regulate the changes being made to human embryos to avoid unanticipated, irreversible genetic consequences for all of humanity.

But what if *mature*, living organisms could be edited—and re-edited? The more I researched that question, the less outlandish the idea appeared. For example, studies using adeno-associated virus (AAV) to spread programmed CRISPR agents through mature organisms have already achieved successes. Most recently a Temple University lab used AAV to lethally edit the HIV virus infecting adult mice—curing the mice.

However, even back in 2015 (when I was doing research for my book) a team at the University of Washington had managed to imbue adult squirrel monkeys with color vision by injecting them with an AAV-based gene therapy.

The researchers injected a mature creature and changed its genetics. From there, the idea of my protagonist having his genetic identity stolen via an injection began to take shape.

Note: Some have suggested that I was inspired by films like Face Off, but Face Off is a story with no basis whatsoever in science. Instead, I arrived at the 'identity switch' conceit by way of developments in genetic editing. More broadly, tales of identity switches go back to Greek mythology, with gods assuming human form to perpetrate mischief. In legend, King Arthur himself was conceived through an identity switch. Later tales like the Prince and the Pauper all the way up to Trading Places continued this archetype. The loss of our own identity is both a terror and a tantalizing possibility, depending on who you are.

What I wanted to do was take recent biotech developments in CRISPR to put a realistic twist on this archetypal tale.

You worked hard to get the technical details right but chose to tell this story as a near-future thriller rather than an essay or nonfiction book about the impacts of synthetic biology. Why is Change Agent a novel? What unique lens does fiction offer on these kinds of questions?

One of the great things about fiction is that it's a license to prototype the future. Unlike a journalist or a scientist, I'm free to write about things as they *could* be—not necessarily as they are. By weaving real and projected science into a (hopefully) entertaining story, I try to make cutting-edge scientific and technological principles much more accessible to a mainstream audience.

My self-imposed goal is to do enough research that a subject matter expert on one of the topics depicted in my books can still suspend their disbelief and enjoy the story along with non-experts. That's tough to do when it comes to subjects like cyber security, robotics, physics, or genetics.

That said, I think novels are still vital in 2017. They permit readers to do a deep dive on a certain topic of interest or familiar characters, and you'll find that a great many popular films and television shows sprang from novels.

Give us a peek behind-the-scenes, what did your creative process look like for Change Agent? When you set out to develop a new vision of the future, how do you go about it in practice? What books have you recently read that changed the way you see the world?

It wasn't that I read any books that *changed* the way I see the world. The catalyst for Change Agent was when I learned about the existence of new, fascinating biotechnologies like CRISPR and synthetic biology. I then went out to educate myself on the current state of that research. In the process I read several key books (which I list in the 'Further Reading' section at the back of Change Agent). In fact, I always include a further reading section in the appendix of my novels because I suspect my readers will be as fascinated as I am by the science behind the subjects I write about.

Of course, I always seek out and interview experts on the topics appearing in my books and often visit key real-world facilities. However, I only do so after I've read widely on a subject. It eliminates the need for elementary questions that waste an expert's time and shows them how serious you are about understanding what it is they do. It also leaves them more time to get to the really interesting stuff.

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Pick up your copy of Change Agent.

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Eliot Peper is the author of Bandwidth, Borderless, Breach, Cumulus, True Blue, Neon Fever Dream, and the Uncommon Series. He's helped build technology businesses, survived dengue fever, translated Virgil's Aeneid from the original Latin, worked as an entrepreneur-in-residence at a venture capital firm, and explored the ancient Himalayan kingdom of Mustang. His books have been praised by the New York Times Book Review, the Verge, Popular Science, Businessweek, TechCrunch, io9, and Ars Technica, and he has been a speaker at places like Google, SXSW, the Electronic Frontier Foundation, Comic Con, and Future in Review.
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