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.

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.

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.