Engineering Life to Work as Expected

What I wrote below highlights some of the risks of engineering living things, the goal of a field called “synthetic biology” . Is anything unclear? Email me! Ask questions! Your advice will make these posts better.
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Microbes growing in lab
We’re at an amazing point in scientific history where we know enough about how living things work to begin tinkering with them. There have been thousands of studies in the last century looking at modifications of living things. At first, the tools we had were crude and the questions we asked were “what happens if make a bunch of mutations in a living thing? What kinds of properties does the living thing show? And what changed in the a living thing’s genes, in its DNA, that caused this change?” As our tools became more precise, so too did our questions. We began to ask what happened when we took out one gene, or added another. “What properties appear when we do this?” we asked. These two ages of research brought is much of what we know about how a genome, a collection of a living thing’s genes (stored in the DNA), work together to create life.
Now, we’re taking this knowledge and beginning to modify genomes with the goal of creating living things that exhibit specific traits, in a field dubbed “synthetic biology”. Want an apple that doesn’t brown when sliced? We’ve got you covered. How about a microbe that produces an extremely expensive anti-malaria drug, making it more accessible? Yep, we have that too. These advances are the products of the last three decades, where concerted effort and millions of dollars bore fruit to create life with an engineered function. But with the ability to do create living things with desired properties, a new problem arose: how do we ensure a living thing we create works the way we intended?
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Sea life grows in a plastic cup washed up during a storm; we may one day engineer life to break down plastic in the oceans
To understand this problem, we have to look at the biological purpose of life. Every living creature has a sole directive: to make more of itself, as many copies of itself as possible. From single-celled bacteria to the complex mass of tissues and organs we call animals, all living things strive to give rise to more of themselves. This directive manifests everywhere around us: the battle for self-preservation, consumption and conflict over resources, the care shown to offspring. It also leads to extreme scenarios, such as when a male spider accepts his death for a chance to mate with a female; in this case, the chance to create more life overrides even the powerful instinct of survival. At every level, in every living thing, this rule acts to reward those that succeed at making more of themselves, as these offspring give rise to more offspring. The winners that are better at following the directive keep winning. The losers disappear from the menagerie of life.
This is where our aspirations of engineering functions into life meets reality. Living things aren’t interested in what we want them to do and our engineered functions are forever secondary to the sole directive of life. Even worse, the changes we make to create these engineered functions are often contrary to this sole directive: they make the living thing less capable of making more of itself. The result is that once we’ve created a living thing with a specific function, such as production of biofuels, it begins trying to undo what we’ve done. The offspring of our living things should have the same engineered functions, but those that manage to undo what we’ve done are better at making more of themselves. In as little as one generation, the function we engineered can disappear. The system is never stable.
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A tree overgrows a wall in Hong Kong. Life has a tendency to escape any bounds put on it.
This is a serious problem because if we engineer a living thing and it doesn’t work as expected, what will it do? In the best case scenario, the living thing loses its function and we’ve got to find a way to get it working again. There are some straightforward ways to do this that I won’t cover here, but basically this scenario just costs some time and money. More worrying is a worse case scenario: where the function we engineered into a living thing to exist within certain limits or parameters, but it breaks free. This is the “Jurassic Park” scenario, where something meant to be contained and safe gets loose and wreaks havoc. And because the function of limiting a living thing to certain parameters is both incredibly useful and directly contrary to life’s sole directive, it’s less a matter of if and more a matter of when this happens. As Jeff Goldblum’s character Ian Malcom says, “life finds a way.”
For those of you now panicking, calling research institutions demanding they stop their work, hang on a moment. You’re right to be worried, and I want you to know that we researchers are right there with you. An overwhelming majority of us are driven to research because we want to do good, and the scenario in which our research creates something harmful is a nightmare. That concern is what drove  a temporary moratorium of research on mutant varieties of the avian flu that could prove more dangerous. It’s what’s behind a push to keep the locations of certain extremely rare animals secret, to prevent poachers from decimating their populations. And for those of us making forays into engineering life, it’s why we’re already thinking about how the functions and safety mechanisms we build could fail, and how we can prevent that. These are the problems that keep us awake at night.
In my case, it’s also the subject of my PhD thesis. I’ll explain that in the next installment.

The Plan

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The best friends in life are those that challenge you to be more than you are already. This is the first post on this blog, answering a challenge from two of my closest friends to lay out plans for a future not yet possible: long-term space travel to other worlds and planetary systems. For this future, we’ll need not only dramatic advances in not only mechanical and energy technologies, but also biological technologies that will support our survival in space. As someone with a PhD from synthetic biology, where we are beginning to engineer life as we can imagine it, I’m going to build a company that will create these technologies. 

This blog is part of that: I will using it to discuss biological research breakthroughs and how they can be applied to help humanity achieve long-term space travel. Below is the rest, a 10-year plan for the future. 

My ten year plan to move from PhD in biology to CEO of a biotechnology company enabling space travel breaks down into three parts: developing business understanding, building startup-related expertise and connections, and identifying problems in space travel that can be addressed with biotechnology. Starting in 2018, I will develop business understanding through my consulting work at ClearView Healthcare Partners. I will focus on working with startup clients for medical and microbiome applications, building my connections and expertise in running a startup. After I settle into my consulting role, I will start research projects in a local DIY bio laboratory to maintain a hand in research connect with talented new researchers.

In 2020, with a perfected view of what we need to make living in space a reality, I will harness my expertise and connections to launch TerraForma, a company that creates biotechnologies for space travel. TerraForma will initiate with two branches of projects: “sure bet” projects with a high likelihood of success and applications to non-space travel (e.g., medical supply and storage), and “big play” projects that are riskier but solve problems essential for surviving in space (e.g., fuel and materials production, self-recycling miniature ecosystems). We will begin with one project in each branch, and expand our project number as our research capacity and funding grows. Revenue will initially come from grants and angel investors, and will switch to licensing for developed technologies and patented innovations within 5 years.

By 2022, the year Elon Musk plans to send humans to Mars, we will have our first commercial technology from a “sure bet” project completed and fully tested on the International Space Station or a private spacecraft. By 2025, TerraForma will bring its first “big play” project to fruition, creating a microbial community capable of either sustained resource production from minimal inputs or a self-sustaining microbial ecosystem that can support animal life. And in 2027, the first of our ‘big play’ projects will be available in spacecraft as a primary support system for human life in space. Past the first 10 years, TerraForma will work to create several self-sustaining biological systems onboard spacecraft, with the ultimate goal of enabling indefinite space travel and making us an intergalactic species.

This blog will stay quiet for a while, as I finish the last six months of a yearlong trip to circumnavigate the globe. That journey is being detailed here

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Biological stars: glow-worms in New Zealand