The Hunt for Wonder Drugs at the North Pole
Gathered around a white plastic table, four scientists surgically explored a quaking pile of mud, freshly scraped from the bottom of the ocean and spiked with twitching tentacles and antennae. In the persistent dusk of an Arctic October, illuminated only by the navigation lights of their ship, the scientists’ orange rubber jumpsuits looked like a collection of traffic cones, bright and reflective against the murky sky. With long tweezers, the researchers organized the mess before them into tidy piles of sponges, starfish, and squirts, delicately picking each out of the morass as if extracting a prized shrimp from a takeout carton of lo mein. I hopped back and forth behind them, trying to stay warm in the biting ocean air and out of range of any sludge flung from the work area. Even in the Arctic, mud is still mud—copious, dirty, and potentially filled with life.
To the 24 scientists on board the Helmer Hanssen, a 209-foot, navy-blue-hulled fishing-boat-turned-research-vessel, the scene was deeply familiar. Most of the members of the team are based in Norway, at the University of Tromsø—the northernmost university in the world—where they are part of a lab called Marbio; the Helmer Hanssen is their home during annual, and sometimes biannual, trips in search of undiscovered organisms. The group is looking for compounds that have novel effects on other living substances, hoping that some of their finds will lead to new, lifesaving treatments for cancer and drug-resistant infections in humans. Their type of mission—traveling deep into rain forests, or to the top of the world, to look for rare, microscopic life—is called bioprospecting. The Helmer Hanssen had just embarked on its 14th bioprospecting trip in half as many years (the 13th was skipped superstitiously), and this time, I had been invited along on the voyage.
Two days earlier, our expedition had departed from Longyearbyen, a utilitarian settlement on the island of Spitsbergen in the archipelago of Svalbard. Halfway between the Norwegian mainland and the North Pole, Svalbard is an Arctic outpost frequented mostly by fossil-fuel experts, adventure tourists, and scientists.
For the first few days, we sailed among Svalbard’s fjords and islands, moving gradually north. Eventually, we would lose sight of land, becoming entirely surrounded by ocean and, later, by ice. Every day, and every mile, would bring us closer to what everyone on board called mørketiden, “the dark time,” the season when the highest reaches of the Arctic Circle receive no sunlight. Our goal was 82 degrees latitude—the farthest north the team had ever traveled.
We would be at sea 12 days, and the work would be continuous: The Marbio team was divided into two watches that worked alternating six-hour shifts, collecting samples by scraping the ocean floor, trawling its waters, and picking its shores. Some of the scientists on board focused on compounds with antimicrobial properties; others were in the business of measuring chlorophyll and capturing microalgae. Four of us had never been on the Helmer Hanssen, but the rest of the scientists were used to the boat and the sea, and attuned to the whims of both. No matter his or her specialty or level of experience, a tolerance of both the work and the waiting was required to scout promise in a brooding sea.
One night, as I sat in the ship’s instrument room with the trip’s bearded leader, Hans Christian Eilertsen, he acknowledged the tough odds of bioprospecting. “It’s very much like looking for a needle in a haystack,” he said with a comfortable chuckle.
For Eilertsen and his colleagues, the gamble is hard to resist. Imagine a starfish the size of your thumbnail, its stubby arms curling skyward like a baby’s. Folded inside the little animal, underneath its knobbly pink skin, are ribbons of DNA and enzymes, millions of years of information stored 15,000 feet below the surface of the Arctic Ocean. For humans, these microscopic structures might be lifesaving—or they might mean nothing at all. The only way to find out is to find the starfish.
For thousands of years, nature has provided humans with medicine. The Ebers Papyrus, an Egyptian text from 1550 B.C., recommended plants, minerals, and other natural products for the relief of everything from urinary-tract infections to wrinkles. At least some of these ancient prescriptions were effective: Honey, recommended for infected wounds, does have antibiotic properties, and coriander, recommended for pain, is a mild analgesic. You probably have at least one plant-based drug in your medicine cabinet. Aspirin was originally made from the bark and leaves of the white willow tree. Taxol, a common anticancer drug, comes from the Pacific yew tree. And nearly a century ago, penicillin was isolated from a species of mold that sprung up, uninvited, in a London professor’s petri dish.
Sixty percent of the drugs we take today were developed from natural products, and most of those products have terrestrial sources. Currently, only seven FDA-approved pharmaceuticals in clinical use have marine sources, compared to hundreds of land-based drugs. And while scientists have isolated more than 30,000 unique organic compounds from marine organisms, they believe there are hundreds of thousands more to be found.
But reaching the bottom of the ocean is a much more labor- and technology-intensive operation than, say, trekking into a rain forest in Costa Rica. Only with the advent of scuba technology in the 1950s were humans able to spend sustained time foraging underwater. And while researchers might need only 50 grams of sea sponge for initial product testing, any commercial product requires far more raw material—and consequently far more time, risk, and cost.
Marbio is one of several international lab groups to take to the high seas, and often these groups pool both their financial resources and their search efforts. Most recently, Marbio took part in PharmaSea, an EU-funded, international consortium of 24 different partners, that collaborated in a search of both warm and cold oceans.
Marbio, however, is a leader among teams working regularly in the Arctic. To survive in extreme conditions, many Arctic organisms have evolved unique and unusually potent chemical defenses, so in theory, products derived from cold-water organisms could be more effective than those from warmer regions. But because human bioprospectors in the Arctic must contend with extreme conditions, too, the search for microscopic life in our cold oceans is just getting started.
Svalbard has a total landmass about the size of West Virginia, but in 2017, its human population was a mere 2,210. Beginning in the 1600s, the largest island, Spitsbergen, served as a walrus-hunting and whaling hub for the English, Dutch, and French, and later was sparsely populated by Russian coal miners. During the Helmer Hanssen’s journey through the archipelago, we encountered the flotsam and jetsam of human activity: abandoned outposts and weather stations, the occasional brick—bright as a flare against the beige scenery—and, of course, lots and lots of plastic. But save for the persistent seabirds, we were completely alone.
On the voyage’s first full day, Eilertsen selected a Ph.D. student named Teppo Rämä and I for a shore-picking voyage. Rämä’s work focuses on the antibiotic potential of fungi, and we would be scavenging the icy beach at the base of the island’s fjords in search of it. Mummified in my heavy, waterproof, yellow-and-blue Arctic suit, I joined Eilertsen, Rämä and a member of the ship’s crew in an outboard-powered skiff. As we ripped toward shore, a walrus surfaced near our little inflatable dinghy, and I was startled by the size and proximity of its huge, tusked head, a boulder rising from the water.
When we reached land, I stumbled while dismounting from the skiff, and my phone fell from my pocket into the cold brine of the ocean, never to be seen again. We had already traveled above the horizon of the satellites that serve mainland Europe, so on the boat cell service was intermittent, announced only by the sudden pings of a slew of missed texts. Now, without even that tenuous link to civilization, I’d have to fully embrace the solitude of the Arctic.
Ashore, Eilertsen and Rämä took off in different directions while I stayed near the armed crewman, mindful of the very real possibility of a polar-bear encounter. Though it was just after lunch, dusk had already fallen. We worked under the pink sky, crouching among frosted rocks and the logs washed up from Siberia, frozen but still fecund. Using his serrated paring knife, Rämä harvested a small, square sample from one of the beached logs, secured it in a Ziploc baggie, and moved down the frost-speckled beach.
To travel so far, and into such inhospitable territory, on such slim hopes may seem foolish, but the need for new drugs, and particularly new antibiotics, is pressing. One recent study predicted that by 2050, if nothing is done to combat the global overuse of antibiotics and the resulting rise of antibiotic-resistant bacteria, infections will kill more people per year than cancer. The implications—for human life expectancy and for society as a whole—are so grim that experts refer to this future reckoning as “antibiotic winter.”
On the silent Svalbard coast, Rämä and Eilertsen traipsed on, filling their baggies with algae scraped from logs and rocks. The beach was scattered with shin-high icebergs laced with holes; jellyfish lay on the sand like so many magenta lily pads. Later, I would ask Eilertsen how he and Rämä knew where to look, and exactly what they were looking for. Eilertsen tried to explain their methods, but acknowledged that they were heavily influenced by circumstances and their inability to control them. “Teppo, he’s looking for fungi on old driftwood, and it’s peculiar,” he said making a that crazy kid face. “But I mean, he could find gold. Who knows?”
Onboard the Helmer Hanssen, the researchers rotated between sampling the ocean and sampling the food. Breakfast was an array of porridges and eggs, meats and cheeses, laid out like an unusually wholesome Vegas buffet. Lunch tended to be warm, hearty, and stew-like, a midday reward for engaging with the elements. By dinnertime, a feast even by land standards, I could usually manage only a small serving of lutefisk and whale meatballs before rolling off to sleep.
After following the west coast of Svalbard for several days, we turned northwest toward Greenland and the open sea, heading for the Yermak Plateau. Though the Arctic Ocean is the world’s smallest, its depth can reach nearly 18,000 feet—more than three miles—in parts of the Arctic Circle, and a plateau on the ocean floor is a rare sampling opportunity. By the time we reached Yermak, the crew’s daily routine was well established: At 9 a.m., after breakfast, the entire group gathered in the instrument room, a communal space where a wall of monitors displayed various updates about the voyage, including a live video feed from the shelter deck where the hauls of ocean mud were raised. During the meeting, Eilertsen, outfitted in his cruise uniform—a black button-up shirt tucked into black chinos, with a baby-blue comb in his back pocket—went over the day’s schedule.
The scuba divers, one each from Greenland, Norway, and Italy, had arguably the hardest jobs on the ship. Though the team used an underwater drone for initial surveys, retrieving specimens required humans, and most days the three men made multiple dives. Every few hours, the crew would also lower a dragging device—part bucket, part claw—from the back of the ship, dredge up a wheelbarrow’s worth of mud, and deliver it to the white plastic table and a group of waiting scientists.
After the morning briefing, half of the crew members returned to their bunks for rest while the rest began a six-hour shift of sampling. At 2 p.m., the watches switched. The Helmer Hanssen had six decks, with bunks scattered among them. My bunk, located in the ship’s bow a floor above on the shelter deck, was a windowless nook with an enclosed bunk bed, a small locker and a plush chair with a foot-long table protruding from one wall. The mess, on the ship’s fourth floor or topgallant deck, was cozy and couch-lined, and every night after dinner, the scientists—one shift putting off going to bed, the other putting off starting to work—would allow themselves an interlude of tea drinking, knitting, and chitchat. During occasional spells of satellite service, we would watch Norwegian prime-time shows like Farmen, a reality show in which contestants are forced to live on a farm with no electricity or running water and compete in games like axe throwing.
The bridge, a quiet, carpeted room ringed with windows, was a refuge from the engine noise and industrial chill that permeated the rest of the ship. It had books and binoculars, and its quiet was only occasionally broken by the crackle of the captain’s radio. The room was the perfect place for staring—by day into the infinite water, dotted with schools of dolphins and spouts of whales, and by night at the northern lights, whose vibrating glow consumed the sky. From the bridge, it was clear that our tiny vessel floated on an enormous ocean, and that the world wasn’t ours. Instead, we were just a few dozen creatures cast among countless others.
Despite the depth and breadth of human ingenuity—our ability to accelerate particles, send men to the moon and rovers to Mars, produce lifesaving drugs, watch American Ninja Warrior via satellite TV on a boat within the Arctic Circle—it’s still difficult for us to outfox bacteria, which can duck, evade, and even fight back against our antibiotic attacks.
One way to outwit bacteria is to sneak up on them incognito, disguising an existing antibiotic by slightly changing its structure. This technique is relatively inexpensive, but risks creating a drug that the target bacteria are already somewhat familiar with, increasing the likelihood of resistance. Another method involves finding completely novel molecules and turning them into drugs unfamiliar to at least some dangerous bacteria. But this practice, as the members of Marbio well know, can be dramatically more difficult. As Jeanette Andersen, the head of Marbio, told me, “you don’t know what you’re looking for.”
The search for the unknown takes lots of time and lots of money: The cost of an average day aboard the Helmer Hanssen is about 200,000 Norwegian kroner, or $25,500. Funding comes into the Marbio lab in a variety of ways, including from the university, the Norwegian government, commercial partners and external grants. And trips must be made with regularity, as even frozen samples can degrade in the laboratory.
After the Helmer Hanssen had returned to port, I visited the Marbio lab in Tromsø, where the team members were beginning to process the hundreds of samples from the trip. They screened each sample to determine its structural information, elemental composition and biological activity, then checked their data against international databases. Had they found a known compound? If so, they returned to their collection of new samples. Had they found a known compound with novel activity? If so, they studied it more closely. Had they found a novel compound with novel bioactivity? If so, their work had only begun. Though years of trial and error stood between the researchers and a new drug, there seemed to be no misgivings about the worthiness of the work.
Since 2007, the Marbio team, participating in a project called MabCent, has spent more than a full year at sea and sampled from over 1,000 different locations around the Svalbard archipelago. They have collected 1,200 different species of invertebrates and hundreds of species of microalgae, totaling more than 3,000 pounds of organisms. And while the work has not yet led to any commercially available drugs, the team has made promising finds, such as a molecule, isolated from a sponge, that has strong antioxidant activity relevant to cancer and diabetes. So strong, in fact, that its effects are now being tested in mouse studies. And gradually, Marbio’s work is helping to narrow its search: Their sample analysis suggests, for example, that Arctic invertebrates have more potential for anticancer compounds, and that fungi are more likely to yield antibiotics.
Bringing a new drug to market—discovering a new compound on land or sea and developing it into a pill ready to swallow—costs, on average, more than $2.5 billion, and takes about 10 years. Even given enough money and time, the odds of success are long: Of the drugs being developed worldwide that make it to clinical testing, only about 12 percent are approved for commercial sale. Antibiotics, which don’t command high prices and can be rendered useless by fast-evolving bacteria, are risky investments for drug manufacturers, who prefer to invest in the research and development of lifestyle drugs. A diabetes medication, meant to be taken every day for the rest of one’s life, is more profitable than an antibiotic created to be taken only in dire situations.
As I walked down one of the lab’s sterile hallways with Andersen, she acknowledged that new drugs are by no means a complete solution to the antibiotic crisis. “I think it would be very naïve to think that we will solve everything by finding a new antibiotic, because we know that it will eventually develop resistance for that molecule,” Andersen said soberly. “But I think we should find new things, because there should be things in development that could be used as a last resort.”
The voyage itself was full of improvisation: The Helmer Hanssen was forced to change course when conditions were unnavigable, and to move on when samples yielded nothing new or useful. The main purpose of our trip was to take advantage of a waning summer thaw to get farther north than typically possible, but when we reached 81.5 degrees latitude, less than 1 degree short of our objective, the team discovered that high winds had packed swirling pancakes of ice into a giant, nearly unbroken sheet. We stood on the deck in the purple Arctic glow, gazing out at an eerily wind-pocked ice field that disappeared into the sky at the horizon in a jewel-toned wash of light.
In order to sample the ocean, the scientists would have to stand on the ice, which wobbled dangerously in the waves. I watched from the deck as the researchers descended to the ice via a rickety gangplank, using shovels to keep their balance and ladders to traverse the shifting floes.
When they reached a fissure, some researchers lay on their bellies, scraping at the ice with small knives, while others jabbed at it with shovels, ad-libbing in the chaotic conditions. After about 45 minutes, the group returned with buckets and baggies of shaved ice, ready to be tossed into the ship’s walk-in lab freezer for preservation. But our stay so far north would be short-lived. The crew had decided that the ice would soon envelop the boat, making it impossible to retreat to open water. That night, the Helmer Hanssen turned southward, and Eilertsen began to plot a new course.
Even though the team had not reached 82 degrees, no one seemed disappointed. The hit-or-miss nature of bioprospecting, and the rarity of a bonanza, generally tempered expectations.
One night, over after-dinner cups of tea during our three-day straight shot across the open Arctic Ocean back to the Norwegian mainland, I asked Klara Stensvåg, a microbiologist, whether the trip had been a success.
Shocked by the suggestion that it had not, Stensvåg folded over her phone’s pink leather cover and began scrolling through her pictures, pausing at an image of an orange ball covered in pimples. “This,” she said, gesturing at the blob. “We had wanted it for a couple of years and at Bjørnøya, we got it.” It was a sea squirt called Synoicum pulmonaria, known for its bioactivity against bacteria, and it had been on Stensvåg’s wish list for a long time. The team had only collected one on this voyage, but as Stevnsvåg said, “Even one is good.”
Bjørnøya—“Bear Island”—halfway between Svalbard and mainland Norway, had not been on the original itinerary; only because of the unforeseen ice conditions had the team decided to make a stop. Stensvåg gazed at the image on her phone, zooming in on it, marveling at her luck. “It felt like an orange,” she said, recalling the moment when the divers, back from another chilly mission, presented her with the little ball.
Any discovery in the ocean, I was learning, required both relentlessness and luck. At one point during one of our evening conversations in the instrument room, Eilertsen confessed, “To be honest, a full cruise can be a waste—but we don’t know that beforehand, so we must continue.” Though always useful in terms of gathering samples, not every trip yielded something novel. “It’s like a lottery ticket you must buy again and again.”
Earlier in the trip, about a week after leaving Longyearbyen, we visited an island named Moffen, off the northwest tip of Svalbard. Flat and shaped like a corona, with a lagoon at its center, Moffen felt like a floating beach, barely breaking the surface of the ocean. In the 1700s, this particular island was a center of walrus slaughtering; by the middle of the 20th century, the walrus population around Svalbard was nearly extinct. In 1983, the Norwegian government protected the island as a sanctuary so that the walrus population could reestablish itself.
Eilertsen insisted we all get off the boat and go ashore. He argued that it was a once-in-a-lifetime opportunity, and besides, we needed the exercise. Once all 24 of us had shuttled to Moffen in the skiff, we scattered, as we were apt to do whenever released from the confines of the Helmer Hanssen. Pairs of scientists turned over rocks, or squatted and examined whale vertebrae the size of Frisbees. A small group of Ph.D. students inspected the frozen body of a dead duck. In the distance, I spotted two seesawing on one of the washed-up Siberian logs. Eilertsen urged us to hurry, which was difficult given that we were wearing our cumbersome survival suits, and full of another enormous Norwegian lunch. The wind gusted by like a passing train, eliminating conversation. We reached a field of walrus bones, the slaughtering ground from generations before. The bones were covered in soft algae, the first green I had seen in days.
After walking for about an hour, we came upon three walruses lying in a row like parked cars. Everyone took selfies with the walruses, thrilled by the encounter. Technically, the researchers were off duty, but they were always alert for something new; for them, the search was eternally on.
“There’s something special about the ice,” one of the Ph.D. students had said to me early in the voyage. “The first time I came up here, I couldn’t sleep. I just stared at the ice.” Everyone who has traveled above 80 degrees latitude seems similarly enchanted. For many, the vast emptiness of the Arctic feels full of potential—of organisms still unknown, of limits not yet reached. That afternoon on Moffen, a place home to wild animals, I understood the spell. Our trip was only halfway over, but already I was missing the Arctic Ocean. The sea belongs to the creatures that swim beneath its surface, not the ones who temporarily float on top of it. But I knew there would be days in the future when I would wish for an excuse to return, to recapture that feeling of frozen expanse, of treasures yet to be found.
Cover illustration by Zoë van Dijk.
Posting of this article is courtesy of The Atlantic. The article originally appeared in Life Up Close, a project of The Atlantic supported by the HHMI Department of Science Education.
(c) 2017 The Atlantic Monthly Group LLC (This article was originally published on the website www.TheAtlantic.com and is republished here with The Atlantic's permission.)
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