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A person is tested for COVID-19 at a drive-thru testing site in Florida in July 2020. Image Credit: Paul Hennessy/NurPhoto, Getty Images

I’ve been exposed to Covid-19. When should I get tested?

Figuring out when to get tested after exposure requires understanding what happens once the virus enters your body. We’ve got you covered.

The bluespotted ribbontail ray (Taeniura lymma) is one of more than 200 stingray species found around the world. Image Credit: Antagain, Getty Images

I got stung by a stingray, and all I got was this deeper understanding of venom medicine

Three years ago, wading in the sun-warmed waters of the Florida Keys, I felt a sharp pinch and looked down at my feet in surprise. My friend Jen and I had driven down from Miami for a weekend full of strong Cuban coffee and Hemingway’s <a href="https://www.hemingwayhome.com/cats/">six-toed cats</a>. Tempted by water so warm and aquamarine it was almost a cliche, we had stopped to swim at a roadside beach on Bahia Honda Key. I had eased in, careful to drag my feet slowly across the seafloor in a dance known to beachgoers as the “stingray shuffle,” hoping to alert any local sealife to my approach. But not careful enough. 
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My foot throbbing, I stumbled back to the beach toward Jen, who wondered if I might have stepped on some glass. But in the next half hour, as my ankle and foot ballooned and the pain ratcheted up—from stinging to aching, from aching to bone breaking—it became clear I must have been stung by something. Then my foot started to turn blue, and we drove to the hospital.“Bahia Honda?” the nurse said. “You’re the fourth person to come in with a stingray sting from there today.”The pain didn’t subside until the next day, when my foot had returned to its normal color. That was the start of a six-week recovery, which also involved crutches, painkillers, heavy-duty antibiotics, and a horrible rash. I wouldn’t wish the experience—which involves a level of discomfort that some have compared to a gunshot wound—on anyone. But in retrospect, it’s an interesting one to consider. Because, it turns out, animal venoms like the one coursing through my veins on Bahia Honda Key are sought after for drug development, with <a href="https://mosaicscience.com/story/medical-menagerie-gallery-venomous-creatures/">seven FDA-approved drugs</a> derived from <a href="https://www.pharmaceutical-journal.com/news-and-analysis/news/from-snake-venom-to-ace-inhibitor-the-discovery-and-rise-of-captopril/10884359.article?firstPass=false">venom toxins</a> on the market so far. Harnessing their power to hurt opens up a world of possibilities for healing.
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<figcaption>The Bahia Honda beach where the author had a run-in with a stingray. Image Credit: Giuseppe Milo, Flickr (CC BY 2.0)
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Chemical biologist Mandë Holford, who studies venom science at <a href="https://holfordlab.com/">her lab at Hunter College</a>, compares what was happening in my foot in the moment after the sting to a “cluster bomb.” The toxins in animal venom have been engineered by evolution over many millennia to incapacitate by affecting some component in the blood, brain, or cell membranes, she says. “You’re getting invaded with 200 to 300 different toxins, all trying to figure out how to reach their target, moving through and rupturing cell membranes, doing all sorts of damage.”The nurse at the emergency room told me stingrays were migrating through the area, their path bringing them close to the cove where I went wading. Stingrays deliver their venom through one or more serrated barbs that lie along their tails. While at rest, a stingray keeps its barb tucked away, immunologist Carla Lima told me in an email. But when it feels threatened—say, by the feet of a clueless human out for a swim—it pushes its tail perpendicular to its body, puncturing that human’s flesh with its venom-laden spine.Lima studies toxins in venomous fish at the <a href="https://butantan.gov.br/instituto-butantan/about-us">Butantan Institute</a> in São Paolo, Brazil. Her research into stingray venom has shown that what’s in that venom actually changes as a stingray matures. In the freshwater species she studies—whose venom properties are better explored than the marine stingray that got me—the venom of young rays tends to contain toxins that cause pain to the target. Lima hypothesizes this may be to chase predators away. In contrast, the toxins in adult venom have a necrotizing effect, meaning they destroy tissue, which would be helpful for hunting.Peptides, short chains of amino acids that play key roles in the biological functions of all kinds of organisms, make up a large part of most animal venoms—and some are only found in those venoms. Lima and other researchers have identified the peptides porflan and orpotrin as two of the elements in the freshwater stingray’s toxic cocktail, along with a number of different proteases, which are enzymes that break down peptides. As I sat cradling my foot on the beach in Bahia Honda, similar proteases and related proteins worked to break down the structure of cells in my heel, helping the venom spread further, and to prompt an inflammatory reaction that led to the swelling I saw. The peptides, on the other hand, likely caused the arteries to constrict and blood to pool, creating more inflammation and blocking circulation—perhaps the cause of my foot turning blue.
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<img alt="stingray under water" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/southern_stingray.width-990_tT3SghY.jpg"/>
<figcaption>A southern stingray (Dasyatis americana) cruises the ocean floor off Grand Turk Island in the Caribbean. Image Credit: Nate Madden, Shutterstock
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That a substance that causes so much pain and wreaks so much biological havoc can be used in medicine is what Holford calls “the yin and yang of nature.” And the fact that damage and healing are, at least in this case, two sides of the same coin forms the basis for the work she does in her lab, identifying new drug applications for various components of animal venom.Venoms have great potential to contribute to drug development because they are both potent and highly targeted, Holford says, with peptides that fit physically into cell receptors and change how those cells function. Thanks to this dynamic, venom-based drugs can work almost instantaneously. And they’re not what people in the pharmaceutical business call “leaky,” meaning they tend to only act on the intended cell component and don’t stop at other spots along the way causing side effects.Most stingray venom research, like Lima’s, takes place in areas where stingrays pose a threat to people: tropical spots like Brazil and Australia. On a drug-development level, we still don’t know much about it, Lima says. But we do know a lot about other venoms—in particular those <a href="https://www.pbs.org/wgbh/nova/article/deadly-sea-snail-venom-could-hold-key-to-faster-insulin-therapies/">created by cone snails</a> and snakes.For one thing, not all venom toxins cause pain. Some peptides present in snake venom focus on manipulating proteins in the wound so blood flows freely, acting as natural anticoagulants. Other peptides in <a href="https://www.research.va.gov/research_in_action/Diabetes-drug-from-Gila-monster-venom.cfm">Gila monster venom</a> promote insulin production, helpful for a hungry lizard that hasn’t eaten for awhile. And yet other peptides in cone-snail venom do the opposite of what stingray venom does: paralyze and suppress pain, keeping the snail’s prey from going into fight-or-flight mode and slowing it down until the (also slow) snail can come nab it for a snack.
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This last type of venom is one of the focuses at Holford’s lab. Many cone-snail venom peptides are rich in cysteine amino acids, whose structure she compares to Velcro. That makes it relatively easy for them to stick in the hourglass-shaped pores on the surface of cells that let important minerals like sodium, calcium, and potassium flow in and out. The free movement of those minerals is part of how cells talk to each other. With those channels shut down, neurons can’t communicate with one another to indicate pain. That’s what makes Prialt, the commercial version of the cone snail’s ziconotide peptide, an effective pain medication. Holford and her colleagues are also exploring the potential of other related cone-snail peptides to help dampen signals firing too fast in someone having a heart attack or an epileptic seizure.She even sees possible applications here for cancer treatment. Current chemotherapy regimens “don’t discriminate between normal cells and tumor,” she says. But because venom peptides work on specific receptors—receptors that some tumors grow too many of as part of their development—they could help create a cancer drug that specifically starves cancer cells of essential minerals, stopping their growth.
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<img alt="snake coiled on rock" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/Echis_carinatus_carinatus.width-990_qUdneyI.jpg"/>
<figcaption>The saw-scaled viper (Echis carinatus) is one of the deadliest snakes in India, and its venom is the basis of the blood-thinning drug Tirofiban. Image Credit: Sagar Khunte, Wikimedia Commons (CC BY-SA 4.0)
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The venom that nearly ruined my Florida Keys vacation (though I still got to enjoy some beautiful sunsets, and the seafood was fantastic) was incredibly sophisticated, honed by evolution to inflict pain and physiological damage with laser precision. It was almost comforting to learn this in the weeks after, as I hobbled around on my crutches and watched with fascinated disgust as the wound developed a stingray-shaped blister. (My boyfriend said it was a sign I was developing superpowers, but sad to say none appeared.)“We know from nature that these peptides work,” Holford says. “What we don’t know is massive: where they work, how they work, how effective they are. And that’s a huge game of ‘Where’s Waldo.’” Holford and her colleagues have come up with a protocol for finding new venom components that have potential in drug applications, then figuring out how to get them there. The first step is a practical look at the natural world: identifying which animal species are creating venom, especially venom that can be extracted manually. Next, the team uses new technologies that Holford refers to as the “omics”— genomics, transcriptomics, proteomics—to identify the toxins within those venoms, by examining the instructions the animals' DNA and RNA contain and the proteins built by following those instructions.From there, the team is able to use that genetic code to manufacture more of a chosen peptide in the lab, which is especially useful when it comes to studying venoms that are produced in small quantities in nature. They then test the synthetic toxin on the animal’s natural prey to make sure it’s effective and further tweak it to ensure it’s as specifically targeted as it can be for humans. And finally, they start to think about drug delivery. Does this drug need to cross the blood-brain barrier? Would it work if administered orally? These are essential questions, since potential drugs that can’t be delivered effectively can’t really be drugs at all.Much like the experience of the sting itself, the possibilities for new drugs here are dizzying. Most venom-based drugs on the market are derived from a single peptide. But my stingray’s venom (just like other naturally occurring venoms) featured hundreds of peptides. And with the advent of the “omics,” drug development with venom has become more efficient. Time- and resource-intensive experiments can now be run much more quickly using computer modeling, making the whole process more viable and opening up a whole world of drug prospects.Lima and her colleagues in Brazil, for example, are continuing to explore the realm of fish venom. One synthetic peptide derived from the venom of a <a href="https://www.fishbase.se/summary/Thalassophryne-nattereri.html">species of toadfish</a> shows particular promise. A <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171796">2017 study</a> suggested that peptide, known as TnP, has powerful anti-inflammatory and therapeutic effects in mice. Effects that could potentially help stem the autoimmune reactions that lead to spinal cord damage in patients with multiple sclerosis.As Holford and her team navigate the new technological landscape, they’re also looking for ways to simplify their process. One innovation Holford is excited about is <a href="https://hsci.harvard.edu/organoids">organoids</a>, in this case, venom glands grown independently in a laboratory. Growing organoids would make acquiring venom samples much easier, she says, and would not require sacrificing an animal for the initial sample. That’s especially important with climate change and habitat loss fueling a looming <a href="https://insideclimatenews.org/news/08042020/global-warming-ecosystem-biodiversity-rising-heat-species/">biodiversity collapse</a> that could take with it undiscovered venoms with the capacity to heal. “In 10 years we’re heading toward this major shift that’s coming if we don’t change our attitudes and lifestyle,” she says. “We could lose a lot of things on the planet that are potentially lifesaving.”
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Animal venoms are useful for drugmakers because they’re potent, targeted, and fast-acting. Trust me, I would know.

Image Credit: Gallinago_media, Shutterstock

What’s the deal with mink Covid?

In the past year, millions of the animals have been culled to stop the spread of COVID-19 on mink farms across Europe. But this is more than just a fur coat crisis.

Less-invasive ventilators use a mask rather than a tube inserted into the patient's throat. Image Credit: Juanmonino, iStock

Covid-19 patients sharing ventilators is possible—but not ideal

On March 20, as severe cases of COVID-19 spiked in northern Italy, emergency medicine doctor Marco Garrone paused during a chaotic shift <a href="https://twitter.com/drmarcogarrone/status/1241135134188937218?s=20">to tweet</a> a photo: two patients, next to each other in hospital beds, with arcs of tubing connecting them to the same ventilator. “This is what we are down to,” he wrote. “Splitting ventilators, and facing serious dilemmas like choosing who will be actually ventilated when everybody should. <a href="https://twitter.com/hashtag/TakeThisSeriously?src=hash">#TakeThisSeriously</a>”A month later, as caseloads skyrocketed across the pond in New York City, Columbia Presbyterian Hospital hurried to draft protocols for ventilator sharing. And around the same time, an emergency medicine doctor in Michigan named Charlene Babcock posted a <a href="https://www.youtube.com/watch?v=uClq978oohY">YouTube tutorial</a> featuring step-by-step directions on how to modify a ventilator so it can accommodate multiple patients. That video racked up nearly a million views in the ensuing weeks.
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“Here’s my disclaimer,” Babcock says to the camera. “This is off-label use of the ventilator.” But, she adds, extreme circumstances may call for measures that otherwise would be deemed too risky. “If it was me, and I had four patients—and they all needed intubation, and I only had one ventilator—I would simply have a shared discussion with all four families and say: ‘I can pick one to live, or we can try to have all four live.’”The appearance of ventilator sharing (or “coventilating”) this spring in places where the novel coronavirus has hit the most severely prompts a number of questions: How does a ventilator work? Why is it possible for more than one patient to use a ventilator at once? And if it’s possible, why aren’t more doctors in hard-hit areas doing it? Good news: This is the first in a NOVA series answering burning coronavirus questions just like these.
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Have a COVID-related question for us? Follow the #CovidQs hashtag on Facebook and Twitter to submit your inquiry or ask us on Reddit @novapbs.
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<h3>How do ventilators work? </h3>Treating a patient in extreme respiratory distress is “like staring out the window and seeing people free fall,” says Albert Kwon, an anesthesiologist at New York Medical College. Doctors don’t know how long their patients have been “falling” or how long they’ll continue to fall without intervention; they must make an on-the-spot assessment about whether a parachute is necessary.In that case, they can choose from several options, ranging from less to more invasive. All ventilators provide oxygen and promote its absorption in the bloodstream while also helping rid the body of the resulting carbon dioxide. The ones you’ve probably heard the most about during the COVID-19 pandemic provide a stream of air into the lungs via a tube inserted into a patient’s throat.This stream of air exerts positive pressure, which is the opposite of how breathing usually works. When we breathe in on our own, our diaphragm muscles move down in our chests, increasing available space and creating an area of negative pressure that causes air to rush in. (There is one ventilator that works on negative pressure, which you’ve probably heard of: <a href="https://amhistory.si.edu/polio/howpolio/ironlung.htm">the iron lung</a>.) 
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<img alt="" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/mouselungs.width-990_k2SexPP.jpg"/>
<figcaption>High-magnification images show the surface of alveoli in healthy mouse lungs (left) and lungs with ventilator-induced damage (right). Image Credit: Kate Hamlington Smith, University of Colorado School of Medicine
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One reason COVID-19 patients need to use ventilators is because their lungs become so stiff that the diaphragm isn’t strong enough to complete its normal movement, causing breathing to slow or stop. Ventilation also keeps the lungs inflated while they heal. That’s important because inflamed capillaries in sick lungs can leak a protein-rich fluid, increasing surface tension in the liquid that normally coats the lungs and making them vulnerable to collapse. But even healthy lungs are at risk during this process, because their tissues are not usually subject to positive pressure. That means that getting pressure levels wrong during ventilation can be dangerous. Too low, and a patient doesn’t get enough oxygen. Too high, and the lungs can become overinflated, causing their tissue to tear.At first glance, the ventilator used in the most severe COVID-19 cases looks fairly simple: a tube that goes down the patient’s throat, two hoses that connect the tube to the machine itself (one for pushing air into the lungs and one for bringing carbon dioxide back out of the body); seals, valves, and filters to keep gases moving in the right direction; and a central case. But inside that case lives a much more complicated device, replete with pressure, flow, and oxygen sensors, and sets of circuitry and alarms associated with each element. A standard hospital ventilator has 1,500 parts, features several layers of fail-safes, and can cost around $30,000. “The number of safeties that have to be on a medical device like this is amazing,” says Nevan Hanumara, a research scientist in MIT’s Precision Engineering Research Group. “This is second only to aerospace.”
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<figcaption>A medical ventilator. Image Credit: Nenov, iStock
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<h3>Why isn’t ventilator sharing more common? </h3>Ventilators have such complicated inner workings in part because ventilation is much more involved than just turning on a hose. The process requires doctors to consider myriad disease factors and patient measurements, making it almost an art rather than a science. "Tidal volume," for example, refers to the amount of air in each breath, "resistance" to the ease with which air moves through the lungs, and "compliance" to how stiff or flexible the lung tissue itself is. Clinicians can also adjust how fast patients breathe and regulate air pressure at each stage of those breaths.All this means that while setting up coventilation is relatively simple—in her YouTube video, Babcock simply uses a cheap plastic adaptor to make space for more hoses—that doesn’t necessarily mean it’s safe. The first problem, Hanumara points out, is that coventilating requires using the same pressure with two very different sets of lungs. The healthier lungs receive more air because they inflate more easily, while the sicker, less flexible lungs won’t get as much.
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Secondly, he adds, sensors calibrated for one person’s measurements may not work for two, meaning the appropriate alarms might not be triggered if there is an emergency. Some COVID-19 patients, for example, experience sudden, catastrophic changes in their lung health; without alarms, it’s much more difficult to catch these changes in time. And finally there’s the matter of cross-contamination. Although two coronavirus patients sharing a ventilator can’t give each other their infections, they might still swap pneumonia microbes, or even tuberculosis.Given these risks, research on coventilation has divided the respiratory care community. Among the more recent studies, Assistant Director of Research at SUNY Downstate Department of Emergency Medicine Lorenzo Paladino successfully coventilated four sheep for 12 hours in 2008. (Garrone, the Italian doctor, looked to that study when setting up his coventilated patients in March.) Paladino and his coauthors chose sheep for their study because adults have similar respiratory physiology and weight as humans, and aimed for 12 hours because emergency protocols allow for delivery of equipment from the Strategic National Stockpile anywhere in the continental US within that time.The study was prompted by the 2001 anthrax attacks and 2003 SARS outbreak, Paladino says, and was meant to provide a stopgap “bridge” measure for emergency physicians with inadequate supplies waiting for backup in a disaster situation—not to replace single ventilation in the long term. Before COVID-19, the technique was most famously used after the 2017 Las Vegas concert shooting, when a single ER saw a huge surge of gunshot patients and coventilated them to keep them alive while they waited for surgery.Paladino compares the technique to a life vest. “We don’t condone crossing the Atlantic in a life vest,” he says. “But if I’m in the middle of the Atlantic, I would rather have a life vest than not. And I would hope that a boat is coming to pick me up soon.”
<h3>The future of coventilation</h3>Not every patient is a good candidate for coventilating, Paladino stresses. Patients with active asthma should be excluded, as should those who tend to “fight” the ventilator, trying to draw a breath when the machine is expelling air, or vice versa. But even with these caveats in place, in the wake of the COVID-19 pandemic, six major organizations—including heavyweights like the Society of Critical Care Medicine and the American Society of Anesthesiologists—have made statements against coventilating, judging it too risky and ethically questionable to be worth considering. “There’s a very legitimate concern that instead of saving two people, you just highly increased the risk of mortality for two people,” says Bradford Smith, a biomedical engineer at the University of Colorado Anschutz Medical Campus. These serious risks point to the urgency of the recent situations in Italy and New York that have led doctors to try coventilation. Smith, who recently published a “preprint” (a not-yet-peer-reviewed preliminary study) suggesting an algorithm to match patients for safer coventilation, runs down the list of options he would try before resorting to the technique: fixing old, broken ventilators; using available machines normally used for surgical anesthesia; attaching endotracheal tubes to similar but less-invasive machines used for sleep apnea. “This is so rife with problems that the first time I heard about it, I thought, 'This is the stupidest thing I’ve ever heard,’” Smith says. “But people are taking steps to mitigate all those issues.”Coventilating practitioners can use filters between patients to help prevent cross-contamination, for example. And protocols drawn up by Columbia Presbyterian and the Department of Health and Human Services (HHS) this spring suggest workarounds to allow for some adjustment of ventilator settings, better monitoring of both patients, and use of some built-in alarms.As in Paladino’s case, most research on coventilation stems from a drive to prepare for the worst. Smith says he was initially inspired to work on his algorithms because he was afraid he would have to use them. (“With the news coming out of Italy, I was on these chain emails of critical care physicians, and things sounded pretty dire,” he says.) And the fact that HHS thought it necessary to convene a taskforce in Washington D.C.—which included Paladino and Babcock—to produce coventilation guidelines for future use speaks to the severity of both the pandemic and predictions for global health over the next two years.Smith hasn’t had to use his algorithms, but he fears fall flu season may provide another opportunity. He also wonders if they may be of use in other places around the world where ventilator supplies are meager, to give physicians and respiratory therapists valuable context about how different types of patients may react to coventilation.“This is not how nations, or even states, deal with a ventilator problem,” Paladino says. Instead, he sees coventilation playing an important role for communities that are rural or isolated, or lack access to medical care. Imagine a small hospital that owns just three ventilators and then receives six desperately sick COVID-19 patients in one night. Then what? “One night you see a spike, and you ask for help from the neighbors,” he says. In the meantime, coventilating just might keep those patients alive.Stream Decoding COVID-19 starting on Wednesday, May 13 at 7/6c on the PBS Video app or online to learn more:
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The science of coventilation for coronavirus cases illustrates a complicated dilemma.

A bald eagle in flight over Colorado. Image Credit: Matt Dirksen, iStock

The unlikely journey of an eagle feather

When an eagle dies in America, it may end up at one of our eagle repositories—unique institutions working to protect both birds of prey and Native American traditions.

Melissa Kemp with a Puerto Rican crown-giant anole (Anolis cuvieri). Image courtesy of Melissa Kemp

Interview: Tropical paleontology and being #BlackInNature

Paleobiologist Melissa Kemp spends a lot of time overturning assumptions. Her excavations don’t involve digging bleached bones out of windswept deserts, but looking for partially preserved lizard fossils in dark, dank jungle caves. Last month, she <a href="https://royalsocietypublishing.org/doi/full/10.1098/rspb.2020.0447">published a study</a> tracking human-driven species introduction in the Caribbean through the region’s 7,000 years of human habitation—challenging the idea that “restoring” Caribbean biodiversity means taking it back to where it was before Christopher Columbus arrived in the so-called New World around 530 years ago. Kemp, who <a href="http://www.melissakemp.com/">runs a lab</a> and teaches integrative biology at the University of Texas at Austin, opened up on Twitter last week about her experience as a Black scientist and outdoorswoman, under the hashtag #BlackInNature—as part of continuing conversations about race in America <a href="https://www.nationalgeographic.com/history/2020/06/history-of-lynching-violent-deaths-reflect-brutal-american-legacy/">following the killings</a> of Ahmaud Arbery, Breonna Taylor, and George Floyd, and the harassment of Black birder Christian Cooper. She spoke with NOVA about decolonizing environmental restoration, tropical fossil quirks, and the joys of time outside.
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Alissa Greenberg: Let’s start with the hashtag #BlackInNature, which you’ve used in tweeting about your love of spending time outside. What’s important about that time in nature for you? What do you feel like it does for you physically and emotionally?Melissa Kemp: I love spending time in nature. I live in Austin now, in a much more urban environment than I was raised in. But it's still very rejuvenating just to go outside and look at the sky, look at the plants, find animals on the property and just see that there's life there. Even when I'm doing my field research, there's bursts of active work where we're hiking through the rainforest trying to get to our site. But then when we get there, it can be very slow. The work that we're doing is very meditative. So nature is very therapeutic for me. It’s played a very important role for me personally and professionally.Particularly thinking about the COVID crisis, so many people are trying to find solace in nature during this time. And I think, now more than ever, it really needs to be accessible to everyone, with everything that's going on—not only to make discoveries in and learn about, but just to enjoy and to feel comfortable enjoying it.
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<img alt="Melissa Kemp tweet #BlackInNature" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/Screen_Shot_2020-06-10_at_3.13.38_AM.width-990_1cTlfyC.png"/>
<figcaption>The hashtag #BlackInNature was used to celebrate Black nature enthusiasts on May 31, the first day of #BlackBirdersWeek.
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AG: You <a href="https://twitter.com/melisabetta/status/1267090009456177152?s=20">mentioned in a tweet</a> that you grew up exploring outside on land your great-great-great-grandfather bought after emancipation. So your family has been there ever since?MK: Yes. I grew up in Maryland, outside of Baltimore. Not really that far from any city, but very, very rural and situated near a state park. And because of that, I had a lot of nature at my disposal. I grew up listening to stories. My mom and my aunts and uncles would tell stories about how they would go out in the woods and explore. So I always had a connection to nature. I never questioned that connection because I felt like I lived in it—even just knowing that my family had been there for so long. The church cemetery was across the road, so I could go in the woods and see the graves of my ancestors.AG: You also mentioned in that same tweet that your grandmother taught you to mark recapture, the biology technique to help estimate animal populations.MK: Especially during the summers when my cousins would be there, and my grandmother had all these kids to deal with, we would go around looking for animals. We always found turtles, eastern box turtles. We would write our initials on them in nail polish, which we really probably shouldn't have been doing, and take care of them for a night, then release them. She would always tell us, “Look for your turtles,” and we would find them again. Sometimes years later, we would find a turtle and be like, “Wait, that's MK, that’s my turtle!” She really encouraged us to just go out there and explore. I think it really rubbed off on me.
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<img alt="Winter landscape painting." class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/Screen_Shot_2020-06-09_at_11.31.24_PM.width-990_7we1xrN.png"/>
<figcaption>A painting by Melissa Kemp of part of her family's property. Image courtesy of Melissa Kemp
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AG: How did you end up working in integrative biology? And why did you choose to focus on islands?MK: I didn't come into science in the most traditional way. When I was growing up, I always thought I was going to be an artist. I went to art magnet schools as a kid and trained at a really high level, mostly painting and drawing. I still approach science in a way that is similar to how I approach art. This diligence of working on something for a very long time and also being open to feedback from others to make the work better. Art is a very iterative process. It can take years before a piece is done, and it's not a sprint, it's a marathon. I think a lot of the same concepts apply to science as well. And my eye for detail maybe helps me find nuances in materials I look at. When I'm working with fossils I'm constantly looking at different shapes and looking for differences in structures of the different fossils I'm handling.I study how biodiversity in tropical regions originates both through processes of extinction and diversification, as well as colonization. Particularly, I'm interested in how changes in the environment then impact the different communities of organisms that we have. I'm interested in these past instances of change that we can see through the fossil record, because it's the key to really understanding the biodiversity that we have today, but also helps us understand how biodiversity might change in the future.Islands in particular are really interesting biologically, and there’s been a wealth of study of diverse life-forms of islands, particularly lizards. But we don't really have as much literature on fossil occurrences of lizards. That's why I started focusing on islands, because we really don't have a thorough understanding of how we got to present day biodiversity.
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Human-driven biodiversity change in the Caribbean did not start in 1492. There is a 7,000-year legacy of change.
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AG: You recently published a paper that delves pretty deeply into that topic. Can you summarize what you were looking for and what you found?MK: We were really interested in investigating how humans have modified the biota of the Caribbean, particularly through which species they’ve introduced. This paper is really thinking about what we are adding to the islands—and what are the impacts of what we're adding? How do those introductions scale across time? We developed a database of species introductions by going through the archaeological literature, as well as the paleontological literature, to get a sense of what we know about species introductions, and then also what we don't know.I think one of the biggest takeaways is the fact that humans have been engineering the landscape for millennia, particularly these places that we think of as recently perturbed. Human-driven biodiversity change in the Caribbean did not start in 1492. There is a 7,000-year legacy of change. We have these terms that I don’t think are representative of the biodiversity of the Caribbean, like “New World.” They're really terms steeped in European colonization, referring back to the Caribbean as something being “new” to Europeans, when people had been living there for a very, very long time.When we think about what the Caribbean used to look like, if you ask somebody on the street that question, they're probably going to think about before Columbus and Europeans came. And we are definitely interested in that period, very much so. But we're also interested in what it looked like before any humans arrived. And we really want to acknowledge how Indigenous groups in the Caribbean moved around, what species they were bringing, how they were using species, and how their manipulation of the landscape changed biodiversity in the Caribbean.
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AG: Why is it important to ask those questions? Not just culturally but also scientifically?MK: We have to be realistic about what's actually feasible. The ideal restoration target probably in the head of a lot of people in the public would be what the environment was like before we came and messed it all up. But it’s not a realistic target, in part because we've lost so many species that were in the landscape before humans arrived.What we see in a lot of systems after an extinction of one animal is that you have an extinction cascade where other things go extinct because organisms are interconnected with one another. They don't exist in silos in the landscape. So, if we remove a pollinator, the plants that were pollinated by it might also undergo decline. They might also go extinct. And that might affect soil erosion, for example. Maybe their roots provided important structure for soil. And if you’re eroding soil, maybe you’re interrupting something else’s habitat. So we would want to restore this system so that that plant is there, and so that that plant is pollinated by an organism in the system—but it might not be possible to do all of those things. So, we have to think about, what is it that we are hoping to accomplish through restoration? 
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<img alt="Paleobiologist in cave with headlamp." class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/Melissa_in_cave.width-990_XKntfYu.jpg"/>
<figcaption>Melissa Kemp excavating a cave site on the island of Marie-Galante, Guadeloupe. Image courtesty of Melissa Kemp 
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Maybe another takeaway from our research would be thinking about introductions of species and what they mean biologically. There's a lot of different terminologies that we use for introduced species—I think one of the most common one is “invasive,” because we often think about the negative impacts of species introductions. Certainly there were instances where species had very, very negative impacts, but then there are also instances where species don't seem to be having a negative impact on the environment and maybe are actually doing good things for those ecosystems.The Caribbean had a lot of endemic mammals prior to human colonization. There were monkeys and a lot of really unique mammals—like these animals called Nesophontes, which are these shrewlike insectivores that are no longer there. We think that a lot of them were really important pollinators in the ecosystem that were then lost. But with the introduction of new birds to the Caribbean, for example, it's possible that some of that loss of pollinators, that ecological service, may have been restored.AG: I’ve read that paleontology in the tropics is particularly difficult. What makes it so hard?MK: The environment of the tropics is not really conducive to fossilization processes. You need stable temperatures, ideally, cold temperatures and dry weather, to get good fossilization—and things covered up really quickly. The tropics are very hot and very humid. It's just so hot, it's so wet, that it's going to erode away very quickly compared to something that's in the Arctic, for example. There's much more rapid disintegration when it's hot and humid. Microbes breaking things down is certainly part of it. Also exposure to UV light—there's physical damage being done to the material as well as biological damage.So we don't have a lot of fossilization in the tropics, but we do have some, particularly in environments where the material is somewhat shielded. Almost all of the work that I conduct is done in caves. We're going through often heavily forested areas, in limestone landscapes where the humidity and precipitation cuts through the limestone and creates cavities. Usually materials get in there through water flow—when, let's say, there's a hurricane.A lot of it is very fragmented bones. We're not getting a full lizard, with the skin removed and the bones in perfect position. Some of them have features that are identifiable, some of them do not. I think that's one of the reasons people have been turned off studying them in the past. A lot you can look at with the naked eye and figure out what part of the skeleton it is, but some of them you need to look at under a microscope.
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<img alt="A tiny lizard jaw fossil in a person's hand." class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/Lizard_fossil_borders.width-990_CB1TvM0.png"/>
<figcaption>A fossilized piece of the upper jaw of a lizard, retrieved from cave sediments on the island of Marie-Galante, Guadeloupe. Image courtesy of Melissa Kemp
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AG: So what techniques have you used to sort of get around those challenges?MK: The biggest thing is just not to disregard the data that do exist and brush it aside. If you want to get material from the tropics, it’s not necessarily going to be very, very flashy in the same way that maybe a T. rex skull would be, but there are valuable data out there. Another thing that we do to get around some of the challenges is we just keep on looking. It requires us to interface with people in that area, talking to people about where caves are, if they've ever seen fossils.So it's very much a community effort, in terms of the work that we do. Finding sites with the help of local people. So local people who are out there exploring the caves for fun often have been a real godsend for us, very helpful in orienting us on the land. They're almost always happy to show us and then interact with us when we tell them more about what we're doing. And that's always really fun.I think it's a function of where I do fieldwork that I have always felt safe in the field. I work in spaces where there are very diverse cultures that are not my own, often cultures where Black people are dominant or brown people are dominant. When I worked in Guadeloupe, for example—a French-speaking island in the Lesser Antilles where the majority of people are Black and Creole—if I kept my mouth shut, people just assumed I was from Guadeloupe. Being an outsider hasn't been a source of fear in those landscapes.
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Just seeing my grandmother as a Black property owner in a small town where there were not many other Black property owners was very inspiring. I don't know if it's the right word for it, but I felt that the outdoors belonged to me and that it was my right to be there. 
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AG: To that end, what’s important about the conversations we’re having now, around the incident with Christian Cooper and the #BlackInNature and #BlackBirdersWeek hashtags? What would you hope might come out of them?MK: It's important because it reinforces, particularly for us as Black people, that we belong here, that this country is ours. We had a very, very instrumental part in creating what we have today in this country, even as we continue to be oppressed. I think it's also important for non-Black people to hear that as well, that they recognize those contributions. I feel very privileged to have had a very positive association with the outdoors all my life. Just seeing my grandmother as a Black property owner in a small town where there were not many other Black property owners was very inspiring. I don't know if it's the right word for it, but I felt that the outdoors belonged to me and that it was my right to be there. I heard messages going through school from other people like, “Oh, nature is more of a white space.” But I really rejected those messages because I had this pride in my family history, and my connection to the land, and my family's connection to the land. I just felt like everyone else had it all wrong, that they just didn't know the history of this country well enough—how tied, for better or for worse, African Americans are to the land. It's a very painful history, sometimes, to think about how many Black Americans got to this country, why we were brought to this country in the first place, to work the land that white people didn’t want to work.For me, at least, learning that history has really made me feel more grounded in the space that I occupy. I've always felt grounded because of my very strong family history. But I know a lot of Black Americans don't have that. Talking to distant cousins that I share lineage with further back, helping them learn about the history of enslavement of our family, has really helped ground them as well.Whenever people may have made snide comments—“I'm afraid of the woods,” or, “The woods is a white space”—I’m very comfortable with my story and being like, “Well, I'm here. My family's here. They've been on this land for six generations. You can't tell me it doesn't belong to me.”This interview has been edited for length and clarity.
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Paleobiologist Melissa Kemp says humans have been introducing species to the Caribbean since long before Columbus arrived—and she’s helping piece that history together.

An empty San Francisco street during the Bay Area's spring 2020 shelter-in-place order. Image Credit: Sharon Hahn Darlin, Flickr (CC BY 2.0)

Interview: A disease modeler talks Covid-19, contact tracing, and quarantine

As the pandemic stretches into its fourth month, it may feel to many of us like we’re eating, sleeping, and living all things “coronavirus.” But in this respect, Rae Wannier outdoes even the most devoted COVID-19 newshound. A fourth-year <a href="https://epibiostat.ucsf.edu/phd-students">doctoral candidate</a> at the University of California, San Francisco, Wannier builds <a href="https://ca-covid-r.info/">disease models</a> using the computer programming language R at the university’s Proctor Foundation. That means she has spent the last few months living the pandemic reality so many of us share—long hours inside, childcare challenges, quarantine birthdays—while simultaneously immersing herself in models of what that reality might become. Wannier, who earned a master’s in public health from Yale University’s Department of Epidemiology of Microbial Diseases before moving west to study disease modeling, worked mostly on modeling Ebola and measles before the COVID crisis. Now she’s helping produce some of the models that agencies like the San Francisco Department of Public Health rely on to make essential decisions about how to react as a community to a largely unprecedented disease threat. NOVA spoke with Wannier about what modeling looks like for her now, the lessons she’s learned from her work, and the importance of fondue in quarantine. 
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Alissa Greenberg: Your situation is interesting because you’re both a private citizen in a pandemic and a scientist studying what it’s like to be a private citizen in a pandemic. So many of us feel overwhelmed with information these days, and you’re probably inundated with information more than most people. But it also felt powerful to read the <a href="https://www.medrxiv.org/content/10.1101/2020.05.14.20101162v1.article-info">preprint [not yet peer-reviewed] paper</a> you sent me, in which you state flat out that 44% of COVID-19 transmission happens before people are symptomatic—to see it quantified that way. Do you feel like the work you do makes you feel more or less in control?Rae Wannier: Because of my work, I probably feel more in control, because I feel a greater degree of certainty in knowing which behaviors to engage in and which to avoid. For example, from this work, I know wearing a surgical mask is much better than cloth. So I make sure to only wear those masks. This work has also made me more willing to engage in outdoor activity, since I know the probability of transmission outdoors is relatively low. I’ve been quite focused instead on limiting any indoor exposure. Having a greater appreciation for the uncertainties here gives me some degree of reassurance, in the sense that I have a better sense of what I can rely upon and what I can't rely upon. And that in of itself, I suppose, is helpful in terms of knowing how I can make plans—as opposed to other people, who don’t understand what's going on and don't know at all what they can rely upon.
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<img alt="Rae Wannier" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/Rae_Headshot.width-990_q34XD5I.jpg"/>
<figcaption>Rae Wannier had worked on models of Ebola and measles prior to the COVID-19 pandemic. Image courtesy of Rae Wannier
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AG: Is that why you got into disease modeling? What do you find compelling about it?RW: I just am fascinated by infectious diseases. I appreciate the logic of trying to understand the transmission and how different behaviors increase the probability of transmission—just the spatial and interactive aspect of it all. With infectious diseases, it all seems a little bit random. And there's this element of chance and probability that's inherent in the whole transmission chain. The interaction between individuals, and often animals, thinking about how people move and when they move and how that impacts this movement of these microbes…it’s just this whole complex network that I find really interesting to study. I also always wanted to study something that I felt was going to make a difference. But I didn't dream that it would become so immediately impactful at this early stage of my career.AG: What were you doing before COVID hit? And how did you decide that it was time to change focus? RW: I've been <a href="https://www.sciencedirect.com/science/article/pii/S1755436519300106?via%3Dihub">studying Ebola</a>, and I have in the last two years personally seen the beginning of an outbreak then become a long, sustained, ongoing outbreak. In those situations, we were humming along, doing our work, and then all of a sudden the outbreak happened and we would just shift gears and start doing forecasting. So looking at this in China, we looked at each other and said, “We don't think this is going away. It's spreading too rapidly.” It only takes a few COVID importations to escape before it ends up becoming community transmission.Now, we've been asked to try and simulate the impact of different interventions and give some advice to the San Francisco Public Health Department on what we anticipate will be the impact of mask wearing and contact tracing and these shelter-in-place orders. Mine is not the only model they’re listening to, but still, this has been a wonderful experience and also an intimidating experience. I want to make sure I have a high level of confidence in what I'm doing, and I'm doing it on a very short timescale with a model that I'm fairly new to. AG: Have you drawn on your previous Ebola work in this research at all? RW: One model I’ve been working on, I’ve used very similar methods from my Ebola work to try and analyze the impact of these shelter-in-place orders on transmission. The way that we've chosen to do it is different than you'll see in most papers. We've broken it down into individual policies. When you think about all of the different travel restrictions that are put on incoming travelers, quarantining them, and putting out rules for increased contact tracing, all of that, it’s a lot of policies. We estimated the impact in aggregate of all these policies is probably to reduce transmission by about 60%. It's quite impactful—like, 60% is a huge reduction. This first paper we’ll publish is a proof-of-concept paper, and then we’re going to extend it to more countries.  
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AG: What can you tell me about that project with the Public Health Department in San Francisco? What’s your modeling work like, and what kind of results are you finding?RW: <a href="https://www.medrxiv.org/content/10.1101/2020.06.09.20125831v1">The model that I've been primarily driving</a> here in San Francisco is using an “agent-based” model to estimate the impact of mass quarantine and contact tracing on continued transmission. With an agent-based model, you actually simulate 10,000 specific people (or “agents”), and you know their gender and their age and where they live and what household they belong to. It’s a toy image of the San Francisco Bay Area. You use census data, what we call “synthetic population,” where within each census tract there are approximately the right number of households and then approximately the right number of people in each household. And then you “infect” people in this population, and what that means is that you have something resembling an accurate network, where we know roughly which people are interacting and how far they're commuting. You can give people very specific characteristics that inform how likely they are to transmit or be symptomatic or die.
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The impact of masks is likely to be felt more as the community reopens more.
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What was interesting, actually—but it makes sense—is that the impact of masks is greatest when community openness is greatest. We think cloth masks probably reduce the transmission potential by about 30% per contact. So it's not actually an overwhelming amount, but it helps. When people are still sheltering in place and there's not a lot of community contact, and workplace contacts are greatly reduced, the opportunity for masks to be impactful is just lessened. The impact of masks is likely to be felt more as the community reopens more. With shelter-in-place, we think cloth masks will only reduce transmission by 8% or 9%. But as the community reopens, that’s likely to increase to 13%. Thirteen percent doesn’t sound like a lot, and it certainly won’t control transmission on its own. But it does help—because it means that you don't have to find 13% somewhere else, from some social distancing measure. And also, if there was the willpower for us to continue to shelter in place, it could drastically speed up the decay of cases and mean that it would shorten the length of time that we would have to continue our current interventions to achieve a halt of transmission.We also found contact tracing is not as impactful as you would hope. By the time you’re identified as a contact and have a test and have a positive result—which is about when contact tracing starts—that's normally four or five days after symptom onset. And most transmission has already occurred before that. Also, more importantly, most of your contacts have already likely progressed through at least half of their transmission periods. Then, when you combine that with the fact that we're only capturing maybe 10% to 20% of cases, you begin to feel less optimistic.The thing that we certainly find with contact tracing is that when you do it badly, it doesn't have much impact. But if you can do it well, like you actually put resources in to do it well—which are a lot of resources—it can have a greatly increased impact. But it's never going to do everything.
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<img alt="People wearing surgical masks on street" class="richtext-image full-width" src="https://staging.pbs.org/wgbh/nova/media/images/iStock.Powerofflowers.1202557009.width-990_5bg0V83.jpg"/>
<figcaption>In modeling the effects of contact tracing and mask adoption on COVID-19 transmission in San Francisco, Rae Wannier and her team rely on assumptions about factors like incubation period, case reporting time, and compliance with mask requirements. Image Credit: Powerofflowers, iStock
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AG: What do you hope the general public will learn from your models? And what do you hope other modelers will find exciting about your work? RW: First of all, I very much hope that they model the same things and with different assumptions and different types of models. What would be most exciting to me is if, with their different models and different assumptions, they come to similar conclusions—because that would actually be the strongest thing that could happen to reinforce our conclusions. We're doing our job right if every model is different. It's very difficult to write a model that considers every single aspect of this ongoing outbreak. Some people focus on underreporting and some people focus on the minutiae of being asymptomatic to symptomatic to maybe no longer going into work, then going into the hospital and every single step of that path. Some people focus on transmission from travel. You can't focus on the minute details of all of these aspects of transmission simultaneously. But each one of those aspects helps inform and guide the response, in terms of helping people understand what parts of this matter. And if you start getting a lot of disagreement, then that's also really interesting because then you can ask: “Well, what are the different assumptions that people are making to get these different answers? Should we be more concerned about this particular part of the disease transmission when we're making these estimates?”Still, the most satisfying part of all this is when you spend a huge amount of work creating this model and coding it and figuring it out, piecing it all together—and then you run it, and it works. Not only that, but sometimes it works and it gives you a result that you didn't expect. And sometimes you think about it, and you're like, “Ohhh, I understand why doing it’s doing that. I hadn't thought about that before.”
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What I have gained the most appreciation for since I started this job is that models are really best designed for relative answers rather than absolute answers. Trying to ask how will this change, not saying, “It will become exactly this.”
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AG: Does it drive you crazy to see all these people on the internet playing around with modeling? What kind of misconceptions does it breed to have all these models floating around?RW: Many people point to models that have gotten things wrong. And part of that is the modelers’ fault. They don’t make a lot of effort to explain what their predictions mean. But I wish that people would maybe have a better understanding that these predictions are not made in a vacuum. These models that we make are only as good as our assumptions, and no model is perfect. If a model is good, its actual goal should be to investigate and question how we expect the dynamics of the disease to change based upon our actions and our choices and the environment that we're in. And that means when they make these predictions, they're going to have certain assumptions about either continuing not to have interventions, or continuing to shelter in place. But hopefully, if we do it right and we pay attention to the model, the bad things that we're predicting will never happen. That doesn't mean that the models were wrong.What I have gained the most appreciation for since I started this job is that models are really best designed for relative answers rather than absolute answers. Trying to ask how will this change, not saying, “It will become exactly this.” For example, people seem not to appreciate that the main expectation is only the mean of a distribution. By which I mean, if we think the mean outcome is 1,000 cases, and the distribution is from 300 to 2,000, we really mean that the distribution is from 300 to 2,000. You should not expect it to be 1,000 cases—because the probability of it being exactly 1,000 is actually fairly small.People do the same thing with weather. They say, “Oh it’s 50%, 60% chance of rain.” Then it doesn't rain and they say, “Oh, they got it wrong.” But the weatherman only said there was a 60% chance; he didn't say 100%. You should actually understand that that “40% no rain” prediction is actually a large probability.We don't pretend that we can say the precise number of cases, especially with infectious disease. Every single person who gets the disease is going to transmit to anywhere from zero to 40 people. Trying to predict whether any individual is a “40 person” or a “zero person,” is nearly impossible. And that is incredibly impactful in terms of the growth of the outbreak—if you get a handful of super-spreaders and suddenly it takes off, or you don't get any super-spreaders for a while and then it grows at a more sedate pace.I don't think that it's impossible for people to understand the concept of uncertainty. But I think that it's been underemphasized in these predictions. Some dedicated scientific journalists actually do a very nice job, but for the most part the lay journalist doesn’t get it right. I sort of wish they didn’t present the mean at all; the mean presents a false sense of certainty. I think if they just said, “They predict between 300 to 2,000 cases,” and just left it at that, then maybe the reader would understand the inherent level of uncertainty here.  AG: Has the hardest part of your COVID experience been professional or personal?RW: The most challenging part has been that I have my son Leo at home with me 100% of the time—while I'm trying to work more than I normally do, and my husband also is still trying to pretend to work full time. Leo turned four recently, our first pandemic birthday. We had a little party; I made fondue and brownies. Tomorrow, I turn 32, and we're going to have fondue. You may have noticed a trend at this point. [laughs] I can’t remember the last birthday I didn’t have fondue.I’ll admit, it’s very hard doing work with Leo at home. I love him, but I also worry a lot about the schools getting opened and closed and what that means to him in terms of not having a routine. The school is still doing a half-hour meeting each day, but the hour changes every week, and my meeting schedule also tends to change.When his school shut down, and they said, “We're going to close for two weeks intially,” I said, “Well, that's a laugh. It's gonna be at least three months.” I knew that going in. But also it’s meant that I have a greater appreciation for just how difficult it is to predict what's going to happen, even once you have very few cases—if we ever get to that point. Or, I should say, we'll get to that point eventually. One way or another, we'll get there.This interview has been edited for length and clarity.
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Rae Wannier is trying to understand the effects of shelter-in-place orders—while sheltering in place.

Alissa Greenberg

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