Biosecurity at the Border

20171111_003139 — Coming in for landing, probably free of biosecurity threats.

THREE hundred and seventy-eight days after my departure on trip around the world, I entered immigration carrying a backpack with some food: a jar of Buglarian pepper spread, a jar of store-bought Italian truffle butter, and a mix of store-bought chocolates and candy from across Asia and Europe. To my knowledge, everything conformed to U.S. Customs and Border Patrol (CBP) regulations, but I had checked the relevant boxes declaring that I was carrying plant and animal products, just to be safe. When the immigration agent glanced at my customs form and asked what I was carrying, I answered and he dismissed me with, “You’re free to go.” When I asked him whether I needed to visit customs, his reply was “No.” Thirty minutes later, I was at customs with agents rummaging through my bags, courtesy of a chance encounter with a cheerful sniffer beagle and his CBP agent near the exit. One of the agents dropped the accusatory line “You should have checked yes to these things on your customs form.” “I did, both on paper and at the kiosk,” I told him, “I even told the immigrations agent what I had.” He was surprised. Everything I had ended up clearing customs, but what if I had been carrying something more dangerous or I had lied? A little dog was the country’s last line of defense, and he was successful only by chance.

To CBP’s credit, biosecurity is hard. I’m not an expert, but to me biosecurity is the defense of the country’s borders against threats to human health, agriculture, or environment, meaning the CPB’s job is to ensure that everyone and everything coming into the United States is “safe”. It requires constant vigilance, like that of a shepherd guarding his flock from wolves or a firewall protecting your computer from attacks. It’s one of those problems where you can succeed a thousand times, but one failure is all it takes to lose. And the price of loss can be huge, whether it’s economic damage or loss of human lives.

I wrote this essay to organize my thoughts on biosecurity at our country’s border, specifically what it looks like now and how it might look in the future. Biosecurity can be broken up into three steps: prevention, quarantine, and mitigation. Prevention deals in minimizing the number of threats that get to our border and includes informing people what can and can’t be shipped. Quarantine is the second step, and should prevention fail, a biosecurity threat should be caught at this stage—this is essentially biosecurity at our border. This is the customs check at airports and shipping hubs, and is the last chance to catch something before it enters the country. After that, the threat is in the country and we’ve got to tackle it with the last step: mitigation, or more simply, ‘dealing with it.’ This includes tracking the threat to understand it, trying to contain it within specific counties or states, and running costly cleanups of areas to try and eradicate it. This is the most expensive and worst step to get to, so efforts to control entry of threats during prevention and quarantine. Prevention often relies on good faith in those importing, because eradication of a pest worldwide is difficult. All this leaves is quarantine, the biosecurity at the border.

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People wait after clearing immigration and customs in Taipei’s international airport. This is the biosecurity border for people and the goods they’re carrying.

WHAT biosecurity at the border looks like today depends on what threat you’re looking for and where you’re looking for it, but it broadly breaks down into searching for threats to agriculture and the environment, or threats to human health. In the first category are a panoply of pests ranging from microscopic bacteria to whole plants and animals, and they can be accidentally transported in everything from soil to fresh vegetables to wood carvings, making detection hard. The second category, threats to human health, is the transmission of anything that might cause disease in people. These threats are most often transmitted by people themselves or through human tissue, although the rising threat of bioterrorism has forced us to consider potential transport outside of the human body, like in glass tubes or sealed envelopes. While the threat of bioterrorism is what garners the most media attention (such as the 2001 anthrax attacks), accidental and intentional introduction of pests are far more costly, to the tune of $100 billion annually. So in thinking of biosecurity, it’s helpful to think beyond the potential for bioterrorism attacks to all forms of potential threats, both present and potential.

But while new biosecurity threats have emerged, the technology we have used to enforce biosecurity at the borders has changed little. The primary way to detect potential biosecurity threats is still sniffer dogs, animals trained to detect and alert CBP agents to the presence of a wide variety of smells. Though sometimes trained to directly smell a biosecurity threat, most dogs are instead trained to detect products that might harbor the potential threat, which then must be verified by hand and in lab. And while effective, these dogs are both expensive and time-consuming* to train and care for. The quality of your biosecurity is then limited by how many dogs you can have and how many hours they can work.

Beyond sniffer dogs, other technologies to detect biosecurity threats either don’t provide enough detailed information or are limited in what they can detect. For example, X-ray screening machines are now commonplace in customs agencies around the world, but their capabilities are limited to distinguishing between the presence and shape of inorganic matter (like computers) and organic matter (like books). In an attempt to detect biosecurity threats to human health, some countries have implemented mandatory body temperature checks of all passengers arriving in the country, but body temperature only rises after the initial stages of infection; a person who is infected can pass through only to become ill and transmit the illness to others afterward. And while detector machines have made their way to CBP to detect specific compounds or chemicals related to explosives, they can’t currently detect biosecurity threats.

Potential biosecurity threats are also becoming more complex and difficult to detect. As the technology sequence and synthesize DNA continues to fall in price and DIY biology increases in popularity, more potential biosecurity threats will arrive in the country in the form of nonliving DNA, the material that encodes the instructions for all living things on earth. DNA that poses a biosecurity hazard is nearly impossible to detect because it is present on nearly every surface of the Earth and is indistinguishable unless sequenced; under chemical analysis, the DNA for poliovirus would look nearly identical to DNA from humans or hamsters. As our technological progress continues, it becomes easier to simply encode weapons of biological warfare into an inert, white powder indistinguishable without complex analysis. But while it’s easy to respond to this potential threat by banning DNA transport or synthesis outright, doing so would wither our efforts to make new cures for diseases or develop helpful biological technologies. We need to balance our freedom to make and move DNA with its potential risks.

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A crane moves shipping containers at the port in Keelung, Taiwan. With increasing movement of people and goods, how do we effectively detect biosecurity threats?

GIVEN the changing landscape of biosecurity threats and our current reliance on older or limited technologies to detect them, what does the future of biosecurity at our borders look like? While I can’t claim to be a biosecurity expert, I can imagine that in the shape of tomorrow we’re going to need biological technologies that both detect specific threats and detect threats whenever anything out of the ordinary appears. We’re now looking to detect three kinds of threats: live things, such as animals, fungi, bacteria, or viruses; dangerous or toxic biological products and toxins, and inert DNA that may encode a potential threat. The best technologies will help us detect both specific threats we know of and help us flag strange things that might represent new potential threats.

There are several new technologies that might help us detect specific threats, including handheld machinery and paper-based diagnostics. When it comes to biosecurity, prevention remains the best option, and potential biosecurity threats are held at secure labs with restricted access, while DNA synthesis companies screen customer orders to determine whether it might encode a potential threat. But this doesn’t protect against individuals or small groups with expertise synthesizing genes/DNA abroad and attempting to bring them into the U.S. Nor does it detect signals that a person may be harboring a dangerous pathogen in their body, either intentionally and unintentionally. A test that rapidly checks DNA sequences for whether they are potential threats, as well as machinery to detect protein or compound-based signs of biosecurity threats would be helpful. In the long run, the shrinking cost and footprint of sequencing means that we may one day have a handheld machine that searches for a panel of sequences that may pose a threat is ideal. In the interim, paper-based diagnostics that detect specific DNA sequences, such as those that can identify different strains of Ebola or detect Zika, appear promising. We could create paper-based diagnostics that bind and signal presence of specific DNA sequences, as well as potentially toxic compounds or proteins.

But perhaps the most exciting advances are in the chance to detect threats without knowing they yet exist. We are increasingly able to sequence microbiomes from a variety of sources, and with some modifications we could extend these technologies to sequence the microbiomes of everything from imported mangoes to dried wood, establishing patterns of ‘baseline’ microbiomes that are present in all safe samples. We could then take samples the microbial populations on all imports coming into the U.S. to screen and match to these baseline microbiome populations, flagging those which show results out of the ordinary for follow-up and barring those that show signs of potential biosecurity threats. This gives us the first chance to detect or identify anything that is “unusual” instead of looking for known abnormal things. While the same thing could be done with people, some serious ethical questions would arise as to who has access to the data, what it reveals about an individual, and what we’re comfortable with as a society. Given these questions, predictive microbiome sequencing is best left as a tool goods imported or carried by people, rather than the people themselves.

When nutria were introduced for fur trapping or Asian carp introduced for aquaculture, nobody guessed that these animals cause millions of dollars in economic and environmental damage. Nobody predicted the SARS outbreak of 2002 or the 2014 Ebola epidemic. We still have difficulty with guessing what new threats lurk beyond our horizon of knowledge, but we’re getting better at predicting which threats on the horizon will be most damaging. By pursuing technology to detect both conventional pests and DNA-based potential threats, to both check for known potential threats and flag unusual changes from the norm, the biosecurity at the border will protect us better.

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*Note: this link estimates the cost of training a dog to detect explosives, not biosecurity hazards per se. I couldn’t find data on the latter, but training a dog to detect biosecurity hazards should be more expensive, because of the wide variety of things they must be trained to detect.

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