The Smallest Self-sustaining Ecosystem: Part II

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The research process, and a preliminary answer

Preface: “AUGHH, SO BORING!” is probably the first response I expect from this post. I can hear the sound of dozens of laptop screens shutting or browsers navigating away to avoid reading this post. It delves into the daunting world of academic and scientific literature, where the English language is changed into some strange, twisted version of itself, lengthened in sentence and peppered with weird acronyms that are meaningless to all but the most entrenched in the field. But reading research literature is absolutely essential to how we arrive at answers, especially in academic fields like the science. And it’s getting easier to do; academic researchers have realized the importance of making their work accessible to everyone, and have pushed to make the language they use easier to understand.

So if you want to get your feet wet in the academic literature, you want a glimpse into what a lot of grad school is about, or you’re just curious about what researchers in the sciences do for MUCH of their time, this post will tell you.

In the last post I defined our question, which was “What is the smallest self-sustaining ecosystem that we could send to space?”. Now I’ll cover where and how to look for an answer to that question in the scientific literature and give a preliminary answer to our question. By the end of this post, you’ll know how to use scientific literature to answer questions of you own!

Diving into scientific literature

Scientific literature can be daunting because it looks unlike anything else we read, but it is the fount of all scientific information. It is the original source of all the information and data, which is collected by news articles and websites to deliver to you, the reader. As with anything involving interpretation, news articles and websites can leave out important information or get things outright wrong when they report on information from the scientific literature, but the only way for you to know is to go read the original scientific article or research report yourself. So if you want to truly know something, read the scientific literature.

We’ll divide our dive into the scientific literature into three sections: searching the scientific literature for research articles, sorting out which research articles in the literature are useful, and analyzing research articles to answer your question. Doing these three steps successfully is difficult and will be slow, especially if you’re new to the scientific literature. Give yourself time when searching the scientific literature and write your question at the top of your page or next to your computer to keep yourself on track.

Step 1: Searching for research articles that might hold answers

In this step I collect several research articles that might have answers to my question to search through in depth later. The best ways to search the scientific literature are Google Scholar and NCBI’s PubMed. Google Scholar searches research articles and primary literature instead of webpages, but works in a similar way to the standard Google search engine so we won’t cover it. NCBI’s PubMed is also a search engine, but it searches all of the primary literature indexed vetted by the National Institute of Health to create a customizable, highly-specific, extensive output. It is the go-to site when I need to find research articles.

Try PubMed by clicking here and typing in something you want to search.

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Search results on PubMed. Each numbered entry in the list is a research article that might hold answers to your question.

Like Google, you’ll see that a search will yield research articles. Clicking on an entry pulls up the PubMed page, which contains the research article information, including the title, author, journal it was published in (which, like magazines have varying degrees of prestige and veracity), and a super-useful summary of the paper called an Abstract that will help you determine if the paper is useful. I prefer to cast a wide net in this step, saving anything that might be useful or interesting to read to answer my question.

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An example entry on a research article in PubMed. Your access to full text links will be the rectangles on the upper right. In this case, the full text is available for free.

If you read the Abstract and think this research article has answers, your next goal is to get the full research article, which is easiest through the “Full Text Links” in the upper right of the PubMed entry. This can get…uh…tricky. In the best cases, the article is free either from NCBI or the journal that published it and the box under “Full Text Links” will say “free full text” or “free final version”, which you can click to get to an HTML or PDF version of a research article. If a full version isn’t available for free (you’ll know because the link you clicked on will say ask for $$ to access an article), then there are a few ways you still might be able to get a research article for free. The first is to check the lab website, which can be done by Googling the name of the last author (here, Pace) and the article’s title–some professors will post PDFs of their research articles on their lab website. A second option is Kopernio, which searches a few websites to determine if the article is freely available. If you don’t find a PDF using these methods, you can also contact an author through ResearchGate or via email and ask for a copy of the article; most authors are happy to share. And the last option, one of dubious legality, is to pirate it from the Russian repository Sci-Hub. Whichever way you choose, save the research articles you can as PDFs into a folder to use in step two.

Step 2: Sorting out which research articles matter

Now you have a pile of PDFs in a folder, one (or some) of which may have the answer to your question. But most PDFs won’t and there are more papers in the world than hours you have to read them, so it’s time to start sorting.

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My file organization system for research. The “not useful” papers usually get deleted, and I go through the “less useful” papers if I can’t find an answer in the papers here. “Round 2” comes from my second round of research (reapeating step 1 again) and I prefer to keep them separate so I know what I have finished reading and need to read next.

I like to sort into three categories: useful, less useful, and not useful. To figure out which papers are useful, I’ll open the file and skim the Abstract, figures, and figure captions — 90% of the time, this is enough for me to figure out if a paper isn’t useful. If I still can’t decide, I’ll read the paper’s Discussion section. If it doesn’t have my answer or any useful related info, it goes into the “not useful” folder. If it doesn’t clearly have my answer but might have some useful info,  it goes into the “less useful” folder. And if I think it’s useful, I leave it in the main folder.

If you happen to find the answer to your question while skimming a paper, that’s awesome! It does happen, especially if you’re looking for a specific fact or statistic. But for more complex questions, you’ll probably need another step.

Step 3: Finding your answer by analysis and synthesis

In this step, you’ll read the articles you’ve found in depth to piece together the information you need to answer your question. This step takes the longest – while the last two may have taken hours, reading through all the papers you think are relevant and synthesizing an answer can take days, or if the question is really big or you’re really new to this process, weeks.

Since this is the long haul, it’s best to start by getting organized. Pick a method of keeping notes, be it on paper or digitally, and stick with it. If you have more than five or six papers, you’ll likely want to keep track of your notes by paper. I use Mendeley to organize my papers, and OneNote to keep track of all my notes on them, including quotes and excepts from papers I’ve read.

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A sample from my OneNote research notes to answer this question.

Now, down to the actual reading. It will take time for you to read a research paper, especially if you’re new at it. Be patient with yourself and start with small steps, maybe reading only one paper a day. If you’re also new to the field of your question, then doubly so– you’ll be learning new words and vocabulary as well as how to read a paper. Look up definitions, write down acronyms on a sheet of paper next to you, and take notes somewhere on things relevant to your question. Try to rephrase the findings of a paper in your own words, which tests how well you understand it. Be patient and steadfast and the papers will grow easier to read.

The last part of this step is synthesis, using what you’ve learned from the research and your brain to make an answer. It’s difficult and will also take practice. Try to answer your question after each paper you read; write it down, read it, and see if there are still missing pieces in your answer. This isn’t a research paper, so your answer need not and should not be a whole essay unless that is what you need to answer your question. A sentence, three sentences, or a paragraph is better if that’s all it will take.

The true test of whether you’ve answered your question is to give the answer to someone else. Take your question and answer to a teacher or friend or family member. Tell them the question and explain the answer to see if you can help them understand. If you’re successful, congratulations! You just taught someone something they might not know. If you’re not or they disagree with you, try to be humble and ask for advice. If they disagree, ask where they get their answer and go look it up. If they ask questions, you can return to the research and dig for more answers. Like an adventurer, keep following the threading trail until you find the answer. It might be something no one has ever answered before.

A preliminary answer to our question, or one is the loneliest number

Phew! The above was an essay I hadn’t originally intended to write, but I started it and it seemed to matter so much in a day and age where there seem to be so many questions that need answers. Thank you if you read through all of that.

I promised a preliminary answer this week and an answer you shall receive!  An early answer to “What is the smallest self-sustaining ecosystem that we could send to space?” is….drumroll please….

ONE (Chivian et al., Science, 2008). Yes, a ecosystem of one was discovered deep in the Earth’s crust. It was found  in a mine shaft in South Africa at 2.8 km deep, or around 933 floors if you take a floor as about 3 meters tall. If you were taking a standard elevator down to this depth, you’d be on waiting in it for a little over two and a half hours.

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The Chivian et al. 2008 paper describing the discovery of D. audaxviator.

The lonely microbe’s name is Delsulforudis audaxviator (we’ll call it D. audaxviator), which as far as I can tell with Google means “the bold traveler of the sulfur lineage.” And it’s capable of living alone because it carries a complete toolkit of genes that help it do everything it needs to survive – helping it ‘eat’ carbon dioxide, carbon monoxide, and formate, ‘drink’ the nitrogen it needs from out of the air as nitrogen gas, and ‘breathe’ sulfate compounds as we breathe oxygen. While we breathe out carbon dioxide, it breathes out hydrogen sulfide gas, which smells of rotten eggs. It’s a one-microbe jack-of-all-trades, do-it-yourself word down there, and D. audaxviator is well-prepared.

So now that we have an answer, are we done? Uh, no. This is a bad answer to our question because it doesn’t meet the rules we set out! Look again at the description of D. audaxviator above. What do you notice? Well, it makes hydrogen sulfide gas like we make carbon dioxide. That’s a waste product. Where is that waste product going? If it just hung around, it would build up. And where are carbon dioxide, carbon monoxide, format, nitrogen gas, and sulfates coming from? If D. audaxviator uses them all up, does it starve? Does it suffocate? This systems fails to meet our criteria of self-sustaining.

If you read the source paper (linked here), you’ll find two things of note. One, many of the things D. audaxviator needs to survive are made from chemical reactions in the earth and somehow either make it to D. audaxviator or D. audaxviator finds them. This same method might be used to sweep away any waste products made, so D. audaxviator doesn’t’ have to worry about them. Unfortunately, we don’t have the luxury of shunting off waste like this while in space. We won’t have the comfort of earth.

The second thing to note in the paper is that while researchers found more than 99.9% of the genetic info from the mine sample comes from D. audaxviator, that is not 100%. There could be some few other microbes living down there, taking the waste products of D. audaxviator as food and turning them into something else. Or maybe they’re taking other compounds and turning them into the compounds D. audaxviator needs to survive. It’s hard to tell for now, and we may not get an answer anytime soon. The researchers couldn’t clearly identify what these other microbes were because there was so much D. audaxviator down there. It’s the majority, and finding the other microbes would be like playing a game of Where’s Waldo, except imagine your book is now more than 2 km deep in the earth and the only chance you get to look at it is through a grainy photograph that’s been fed into a shredder and then put back together again. It might be a while before we get an answer.

So we found an answer to the question, but it’s not a very good one. Let’s follow the trail of research using Step 3 to find a better answer.

Followthetrail

The smallest self-sustaining ecosystem: Part I

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Ecosystem in miniature: A mushroom grows among moss and decaying pine needles on the forest floor. (Lahemaa National Park, Estonia)

Life on Earth is complex and if we want to live out in space, it’s unlikely that we can take every species with us. Our ventures off-planet have carried only the bare necessities and due space constraints (pun intended), that’s unlikely to change in the near future. But constraints breed creativity, so to honor that spirit let’s look at what we small groups of species we can send off into space that would continue to survive without the umbilical cord of earthly supplies. Specifically, our question is:

“What is the smallest self-sustaining ecosystem that we could send to space?”

That’s a tough one, so we’ll start by defining what we mean in this question. First, let’s tackle the meaning of ‘ecosystem’. This is the word we use to encompass many different species living and interacting with each other and the nonliving components of their environment. This is the mix of all the microbes and trees and animals in a rainforest, combined with who eats who and conditions like the amount of rainfall or sunlight available. It is the tiger that eats the deer that eats the leaves, who dies to be eaten by the worms and microbes, who make the dirt to feed the leaves to feed the deer to feed the tiger. This isn’t merely poetic, it’s the literal passing of matter and energy, physical stuff and the power to move it, between individual parts that comprise the ecosystem.

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Simple Ecosystem: dead plant matter (a log) feeds moss and fungi, which in turn feed a fly that will die to become food for more plants. (Bialowieza Forest, Poland)

Now, let’s move on to ‘self-sustaining’, the hardest part of our question. We want our ecosystem to continue without supplies from Earth. Is that even possible? Hypothetically yes, but it depends what you mean. Earth itself survives without supplies from elsewhere, passing matter between the living and nonliving in ecosystems – in this sense, Earth is a closed-loop system, moving physical stuff, matter around without gaining or losing matter from an outside supply*. But that’s just matter. Energy is a different story; the sun constantly supplies Earth with energy that flows through ecosystems and eventually dissipates back out to space, mostly as heat. So if we’re talking energy, Earth is an open-loop system, constantly being supplied more energy.

While it would be amazing to make an ecosystem that is both closed-loop for matter and energy, the problem with energy is that it decays into ‘useless’ energy like heat that cannot be used by life. Yes, I feel that irony writing from -10C temperatures in Boston, but it’s scientifically true. So for our question, we’ll aim to find an ecosystem that’s closed-loop for matter, but gets an energy supply from elsewhere. Even this is a hard problem; Earth is huge and while individual ecosystems are mostly ‘closed-loop’ for matter, they’ll shunt waste products off to other ecosystems to use. In space, we won’t have that luxury. Any waste made in an isolated, spacebound ecosystem must be used by something else in that same ecosystem.

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Stuck in the bucket: matter usage in a spacebound ecosystem would have to be almost entirely, if not totally closed-loop. (Banks of the Danube in Budapest, Hungary)

And lastly, what do we mean by ‘simplest’? We could say that ‘simplest’ just refers to the fewest number of different species in our ecosystem. After all, fewer moving parts that can have something go wrong is better, right?  Or we could say that ‘simplest’ refers to how complex the species in our ecosystem are, meaning we’re looking to work with the simplest parts we can get. This would be microscopic life like bacteria, amoebas, fungal yeasts, cyanobacteria, and single-celled algae, which have the benefit of being small as well as ‘simple’.

Finally, we could take a step back and erase species from the equation and instead say the ‘simplest ecosystem’ is just the fewest number of chemical reactions to keep matter moving through the environment when you add energy. This is like cutting away all of the walls and membranes on cells and just looking at their metabolism, what chemical reactions they are running to convert starting reactant A into finished product B. Another reaction then need to take B and make C, and a third reaction then takes C and makes A. For now, we won’t settle on a specific definition of ‘simplest’, but will keep all of these in mind as we look for the simplest self-sustaining ecosystem.

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A “simple” ecosystem with only a few visible species may have thousands more unseen microbes carrying out complex chemical reactions. (Bialowieza Forsest, Poland)

Speaking of, where are we going to look?

Good question! Stay tuned for Part II, in which we’ll speculate on where to start looking for  the simplest self-sustaining ecosystem.

Making sense of the mess: creating stories to understand

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I start my first consulting job this Monday, working with a healthcare consulting firm to help companies solve real-world problems. Before this, I was PhD student working in a research lab and my consulting experience was only pro-bono projects with a graduate consulting club. Nor was I terribly close to the healthcare field—my lab doesn’t do research on anything directly related to healthcare of pharmaceuticals. Given this background, you might be asking how I can possibly work in healthcare consulting. There’s so much I don’t know, how can I possibly succeed? Where do I possibly start learning?

When faced with a huge field containing a lot of information, I’ve found the best way to start learning is to build stories. The human brain is wired for stories because it naturally creates or attributes agency to things. It finds causes and effects. So we can use this innate understanding of stories to go into a field and build a narrative that helps us understand. Think of the story of Newton and the apple during discovery of gravity. Whether or not it’s true, we remember that an apple fell onto Newton’s head and he realized gravity exists. There’s a cause – the apple – and effect – Newton suddenly ‘getting’ gravity as a force that pulls things toward the Earth. In learning this story, we remember more than if someone had simply told us “Gravity pulls things toward the Earth.”

But in a new field, it’s not enough to simply hear the story. It’s the act of making that makes you remember. To truly understand something, build the story yourself. As an example, this isn’t my first field switch; before my PhD in synthetic biology, I got a B.S. in Environmental Science. But the those two fields are far apart, so I built stories that covered the major breakthroughs in synthetic biology. I looked at who had done what and when and who built on that research afterward. It helped me rapidly catch up and graduate on time with my peers. Science also backs me up on this one: writing, or more broadly just interacting with information beyond reading it silently helps you remember it (Sources: PopSci article, Hardcore paper source from recent literature).

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An example of a timeline made in Sutori (link below) to help understand companies in the healthcare industry.

So if you’re jumping into a new field or subject, don’t just passively read stories, make them. How? There’s always pencil and paper, where you can draw a timeline or write a paragraph-long story summarizing what you’ve learned. But if you want something searchable, try making your story digitally. I’m currently using Sutori, which lets you create timelines for free using any kind of mixed media (text, image, video). There are also several other timeline builders listed here, and you can even organize information beyond the timeline and make a flowchart or sketch on Google Docs, Microsoft Office, or wherever else you can find the tools to sketch and write. Get creative, because the more you create, the more you’ll remember.

So feeling lost in a new field? Start making a story out of it.

Biology x Classification: An instructional on species

It’s been a while since I updated, thanks to the hectic nature of moving to a new state, driving across the U.S. for a third time, and getting settled before I start work. Here’s a cross-post from a project inspired by my friend Cindy Nguyen. She runs Haptic Press, a creative arts labspace for anyone to looking to experiment with creativity. Especially those people who haven’t done something ‘creative’ in ages like *cough* me. Graduate school was an eternal summer for my mind, but it was a long, dark winter for the creative self.

This piece is in response to Cindy’s most recent theme, “Classification”, merged with what I know to become “Biology x Classification”. This is a tribute to how messy life is, despite our best attempts as scientists to classify. Hope you like it.

An instructional on species

step one: definition

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Figure 1: An individual

what is a species?
do you know?
Can you look up the definition?
Go ahead. Do it now.
i’ll wait here.

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Figure 2: A lineage




have it? Read it out loud
And clear,
for both of us to hear.
Awesome.

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Figure 3: Two descendants, one ancestor

now, things get fun.
imagine the definition in your mind,
like on a piece of paper.
Take it, tear it up,
And toss it into the wind.
make a mess.

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Figure 4: A mess

step Two: mess

The truth is, a species is messy.
it’s messy just like the scattered paper
That now makes up our definition.
you may have looked at animals and thought,
“This duck is different than a cat,
which is different than a deer or a bat.
All different species.”

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Figure 5: Shared ancestry

And you’re right.
we can tell very different things apart.
but what about this bat and that?
This lizard and that?

The closer the two animals get together,
The harder to say they’re a different species.

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Figure 6: Species complex, wherein ring species interbreed

we biologists like to say if animals don’t breed,
meaning they can’t make offspring together,
They’re different species. Separate.
but there are species of lizards that blend,
from one place to another.
Able to breed with neighbors,
And neighbors-neighbors,
but not neighbors-neighbors-neighbors,
And more distant.
so where does one species start,
And another end?

hard to say.

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Figure 7: Interbreeding fails at ring edges

step Three: mix

or look at bacteria,
That make offspring only by dividing.
how do you decide a species
in a thing that does not mate for offspring?
who is to say bacteria A is a species itself,
isolated and separate from bacteria B?

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Figure 8: Asexual reproduction

well, we tell ourselves that it’s in the DNA,
The genetic information that makes all life.
we look at two bacteria,
And if the DNA is different enough,
(we say 1%, but where does that come from?)
we say Bacteria A and B are different species.

but it gets even messier in the bacterial world,
like the pieces of our definition swirling in the wind.
because bacteria can mate,
They just don’t make offspring.
They mate across species,
Across close relatives and distant friends
not to make more of themselves,
but to swap DNA,
The very basis of our definition!

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Figure 9: Horizontal gene transfer

They share DNA in mating,
Copying and swapping like teenage pirates,
a gene here, sequence there.
Copy, cut, share, paste, repeat.
each action blurring lines:
is the new cell, now carrying a bit of species A
still species B, or something new?
who’s to say.

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Figure 10: Which species, none, or both?

step four: matrimony

And then there’s you.
The collection of cells you think you know
All descended from a first.
but beside your human cells are the others,
A collection of millions by millions of bacteria,
on your skin, in your gut,
on every open inch of body.
The unseen multitudes of multitudes,
different between each person.
They make you, become you,
Are you.
so you are what?

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Figure 11: Human and microbiome

And where do you come from?
who are your ancestors,
your mother’s mother’s mothers
stretching back into unconscious unmemory.
A secret, hidden in you
Thousands by millions of years ago.

Chance cast her lot,
As one cell engulfed another.
A normal act of eat to live,
but this time the infinitely unlikely,
Completely unguessable happened.

The devourer did not kill to sate its hunger
And embraced instead the cell within it
As a host would a guest in their home.
The guest, sealed and safe from the surrounding world,
gave energy for life in return.

if you seek within your cells,
you find these once-guests still today.
making, providing, trading
Their energy for a home.
The two working together,
Creating life from mice to men.
That is the strangest thing about you,
descendent of that accidental chance.
you are a marriage of not one form of life,
but two.

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Figure 12: Endosymbiotic theory

step five: reality

As you can see, the definition of a species
diverges between flat paper and life.
our paperbound sentence is just convenient shorthand
hiding a stout, immovable truth.
for it’s impossible to encompass the chaos of life
of even for an individual in a word.
A name, a handle, a term,
falls short.

And life’s lineage stretches long.

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Figure 13: The lineage of life

Biosecurity at the Border

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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.

*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.

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.”

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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.

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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.”

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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.

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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

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A sandy beach in New Zealand

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.

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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.

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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.