Synthetic Biology and Social Discomfort

On the way home from mushroom hunting, someone in the foraging group asks what I do for a living. That’s a tricky question. I could respond with the research I did for my PhD, which would be something like “biology” or “bioengineering” or “synthetic biology”, but none of these answers hold much meaning for people. So I go for the simplest answer that’s interesting. I tell them, “I built life.”

20160618_115442 — Some of the living things I’ve built.

I’m not exaggerating. My PhD was five and a half years working on engineering organisms that would improve human lives while using less of Earth’s resources. That goal is hundreds of separate projects in several lifetimes of work, so I focused on the part that serves as a lynchpin to them all: if we create a living thing with a function, how do we ensure it works as intended in complex environments? Like the plastic insulation protecting electrical wires, engineered life needs an isolating barrier protecting it from the surrounding natural life that could cause a short-circuit and stop working. Physical isolation tools exist, but they need to be maintained and have limited use. So for my PhD I engineered genetic isolation directly into cells, an insulation that they always carry with them. This genetic insulation protects the engineered cells from nature and vice-versa. And it means that we can one day use these engineered cells to create medicines, renewable energy sources, and environmental protection and repair systems.

IMG_20170307_092224491 — A forest in Australia. It’s one of the many ecosystems I hope to preserve by creating living tools that help people live with more while taking from the environment less.

Back in the car, the response I get from the group is a mix of awe and horror, which is normal. Because I’m with a group of foragers, I can accurately predict the next step in the conversation. “It is just my opinion, but I don’t think we should be changing life, messing with it,” says the man beside me. I nod politely. Though the old knowledge of traditional cultures and new knowledge of academic research are entirely compatible and built on the same scientific methods, a mutual distain keeps the practitioners of these two camps aligned against each other. As scientist of academic research, I’ve lived this conversation a thousand times already. But it’s an important one, and it’s not about me convincing this guy that his opinion is wrong. It’s about understanding why.

By and large, people are uncomfortable with engineering life because they consider it special. We divide the world into living and non-living, and then spend much of our memorable lives interacting with the living: family, friends, pets, nature, food. We consider there to be some mysterious spark to life that we haven’t figured out, both philosophically and scientifically. To say you’re changing living things naturally raises hackles; the assumption is that in order to do that, you must have sacrificed your belief in the sanctity of life. That you don’t care about the consequences. Or, as quoted from Jurassic Park: “so preoccupied with whether or not [you] could, [you] didn’t stop to think if [you] should.”

Life is pernicious and controlling it can be hard: here, algae grows on the inside of a plastic cup on the beach.

But the truth is that we scientists think constantly about “whether you should.” It is the undocumented part of our lives, the part spent away from the laboratory equipment that everyone associates with us. In this time, four sources prompt us to consider the meaning and significance of our work. The first is from ourselves; as we’re naturally inclined to think (and overthink), we find ourselves imagining scenarios in which our research could be misused or go awry. The second is our peers and colleagues, who carry a mandate to question our work and ensure it is safe. The third is in grant proposals, where we meet the scrutiny of scientists and policy-makers who fund our work. And the fourth is in scenarios like the one occurring right now in the car, questions from our communities. Every one of these sources drives us to think about the impacts of our research and what could go wrong.

Yes, the conversations I have with people about my work “building life” can be uncomfortable. It’s not fun when someone tells you that your life’s work is objectionable, distasteful, an affront to society, or a one-way ticket to hell. But these conversations are important. They tell me what people are worried about, and by extension, what I should worry about in my work. These conversations are also a brief chance for me to explain how much we scientists care about the impact of our work, contrary to scientist stereotypes. It’s not easy, but somebody’s gotta do it.

My research on creating genetic insulation for engineered organisms. If you leave here with one thing, know that we scientists hear and share your fears. It’s why we do research.

[This is a cross-post from my current main blog, Neverending Everywhere, where I document travelling around the world.]

Science Oddity: The USDA doesn’t regulate sand from ocean beaches

Moving soil between countries is hard. Back when I worked in a soil microbe lab, my colleagues lamented the effort and paperwork required to import soil samples. If they wanted just the soil, they had to ask the sender to sterilize it using USDA-approved methods to kill any potential nasties that might invade the US and cause trouble. And if they wanted unsterilized soil to study the live soil microbes, they needed to apply for two different USDA permits. That meant taking precious time to submit paperwork justifying why you want the soil, how you’ll use it, and how you’ll keep any microbes in the soil from escaping.

This might sound like an unnecessary burden, but these regulatory hurdles are a vital part of keeping the US safe. Soil harbors microbes, insects, and plant seeds, including those of pests that if introduced could do serious economic and environmental damage. One study found that introduced pests and invasive species cost us nearly $120 billion annually. These include the citrus greening disease, responsible for stunting and killing citrus fruit trees in Florida and costing the state’s iconic industry $4.5 billion between 2007 and 2011. They also include pests like the soybean cyst nematode, which cost soybean growers $500 million a year and originally arrived in the U.S. via imported soil. Then there are the Zika and West Nile viruses, recently introduced diseases transmitted by people and now established on the US mainland. With any pest, it can take as little as one accidental release to unleash destruction. The stakes are high.

So it floored me when during a marine biology project, I learned that mailing ocean beach sand was essentially unregulated by the USDA. At the time, I was researching the effect of agricultural waste on reef health on the Society Islands and spent hours a day snorkeling in a fetid part of Cook’s Bay just below a goat farm. Near the project’s end, I asked our graduate student advisor how to prepare samples to ship back to the U.S. She told me to just seal them in an airtight container and they were good to go. “Do I need to sterilize it?” I asked. “Nope,” she replied, “the USDA doesn’t require it.” I ended up not shipping sand back to the U.S. for analysis, but if I had it would have carried the microbes from the goat farm runoff, potential pests and biohazards and all. Then again, I had just spent six weeks swimming around in diluted goat feces—I was probably a biohazard.

Rocks on a beach in Japan; according to USDA regulations, you can bring these back to the U.S. as long as they’re free of organic matter, though they may still harbor microbes.

To this day, that USDA still technically does not regulate the import of ocean beach sand, so under this loophole you can ship the uncleaned “sediment of saltwater oceans” (i.e. sand) without any permit. Note that this doesn’t apply to the sand/sediment of inland saltwater seas or freshwater lakes. But how could the customs procedures be so different for soil versus ocean beach sand, or beach sand from the Mediterranean Sea vs the Black Sea, separated only by the thin Bosphorous Strait? Ostensibly, the reason is because all of the saltwater oceans in the world are connected, so they already share the same pests and importing beach sand won’t introduce new ones. But this logic ignores the possibility that beaches might harbor different microbes (and potential pests) due to influence from microbes in nearby land soil or human activity (like a goat farm). And while the Customs and Border Patrol (CBP) have tried to discourage people from bringing potentially contaminated sand back to the US, they also acknowledge that due to the USDA’s loophole, you’re free to bring uncleaned ocean sand back with you as long as it doesn’t have visible chunks of organic matter (like twigs or dirt).

But should you? I’m not so sure.

Customs and the USDA won’t allow you to import organic matter, like this dried piece of algae. But they don’t have rules against importing the sand around it.

What I learned by starting this blog

The endless sea of ideas beyond the bramble of writers’ block

Hey reader!

It’s been a while since a post, hasn’t it? I’ve learned a few things in starting this blog that I want to share with you below because I’d wager a lot of people face similar problems. If you’ve been stalled on your blogging/writing, I give you 100% permission to borrow this post, blame it on one the problems below, and start anew:

Writing what you know well isn’t always the easiest. You get bogged down in the details and you want it to be perfect. This is compounded in academia because you worry about the balance between reaching people outside of academia and those who might read it in the academic circle. To make blogging easier, begin with subjects you know some about and you won’t be dragged down into the deep details. Yes, sometimes you’ll write things that won’t make sense later or might be wrong, but that’s FINE. We learn nothing by venturing nothing.
Don’t feel beholden to a post you said you’d do, and you can always postpone a post to later. This is a hard one for me because I feel strongly about commitments and following through. It’s the same feeling that gives us anxiety when we leave an email unanswered for what we think is ‘too long’ or haven’t posted on a blog in a while. You feel like you’re letting your audience down, whether it’s one person or a million people. But you don’t owe the internet anything—you’re a free person.
This is an extension of 3, but it’s important to say on its own: write what you want. The easiest way to kill a blog is by having writing ideas but putting them aside because you “said you’d do” a specific post next. Likewise if you’re writing just for likes/favorites/exposure. It’s going to feel like an awful chore if you don’t write about what you want, so write about what you’re interested in, what you want to learn about, what won’t leave your mind. Get your thoughts out into the world.

So I’m holding off on writing in-depth about my PhD work for now. But I also didn’t want to be beholden to #1, so I wrote you a six-sentence summary of what I did in my PhD. Is it perfect? No. But it is:

As I described in the previous post, if we want to use living systems (organisms, cells) as technology, we want them to work as expected because we can’t rely on them if they don’t. One of the biggest problems is that most of life uses the same genetic code, so engineered cells can pick up genetic information from the environment that messes with their intended function. It’s as if we were all running the same version of Windows; you could install a program on any of our systems and it would run–including viruses and malicious code. To solve this problem, my PhD showed that changing the genetic code of an engineered cell makes it harder for genetic information in the environment to mess with the cell’s function, making it more stable. It was like we modified the “operating system” in our engineered cells, making it harder for malicious pieces of genetic information such as viruses to infect. In the future, we can change the genetic code in living systems to ensure they work as expected, bringing applications of biotechnology and synthetic biology closer to realization.

What will I write about next? We’ll see what I feel like, although posts will probably remain infrequent while we travel around the world (more on that here). One of the big projects I want to do over the next year is learn the physics of aerodynamics and orbital mechanics, partly because both of these are really important for space travel and partly to dispel the persistent myth that you can’t transition from “softer sciences” to “harder sciences” later in life. Anyone should be able to learn anything regardless of their background.

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.

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?

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.

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

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.

Biological stars: glow-worms in New Zealand