Cool Jobs: Diving for new medicines | Science News for Students

Cool Jobs: Diving for new medicines

Researchers swap lab coats for wetsuits in the search for new drugs to treat disease
May 3, 2018 — 6:45 am EST
Reef diver

Life beneath the sea surface can be lovely and lively. But many organisms there produce toxic chemicals to fend off predators. Divers are now collecting such poisons as candidate drugs for human medicine.

paulbcowell/iStockphoto

Sharks aren’t the scariest things in the ocean for scientists who dive to work. Powerful currents, created where the ocean floor drops away, can be just as deadly.

“You can get sucked down and crushed by the pressure within minutes,” notes Marcel Jaspars. He’s a chemist who once saved himself from such a current. He encountered it while taking photos of a sea sponge near Indonesia, in Southeast Asia. Luckily, he inflated his dive vest in time. He was able to float to the surface and escape the potentially deadly current.

Polynesia sharks
David Gruber and his team meet sharks while diving in French Polynesia. 
Rodolphe Holler

Diving has risks. But the scientists who work underwater train to deal with these dangers. For Jaspars, the rewards of research and underwater adventure are greater than the risks. He searches for unusual chemicals made by ocean life. Then he analyzes them for ingredients that might serve as medicines for people.

The sea may seem like a strange place to look for new drugs. But organisms in the ocean have had to adapt to a tough environment. Some of the chemicals they make for survival might help people, too. More than 50 years ago, scientists discovered a new anti-cancer drug in a sea sponge. Since then, researchers have been hunting the seas for more of such useful natural products.

With the help of underwater robots and small submarines, Jaspars and other scientists are searching the seas — from shallow reefs to the oceans’ great depths. Their goal: finding chemicals made by marine life for use in one day treating human disease.

Diving deep

Marcel Jaspars
Chemist Marcel Jaspars combines his love for diving with the study of unusual molecules made by marine life.
Courtesy of M. Jaspars

Jaspars’ research has taken him from the bright blue waters around Indonesia to the Red Sea (south of Israel, and bordering many African nations). He got hooked on diving after watching television shows about ocean explorer Jacques Cousteau. By the time Jaspars was 16, he had earned his certification to dive in the cold waters off Great Britain. Later, he studied chemistry and biology. Those studies now help him figure out how to turn marine molecules into human medicines.

Consider sea squirts. These soft, boneless animals anchor their bodies to the sea floor. As they pump food-laden water through their bodies, they filter out any bits they can eat. Certain squirts on Australia’s Great Barrier Reef also make chemicals that can kill human cancer cells. (The chemicals probably help the squirts defend themselves.) Jaspars helped figure out how to get bacteria in a lab to produce the same chemical. This let scientists study the chemical without collecting — or harming — any wild sea squirts.

Now Jaspars directs the Marine Biodiscovery Centre. It’s at the University of Aberdeen, in Scotland. There he focuses on microbes living in very cold environments, such as the Arctic Ocean. “It’s too cold and deep to dive there,” he says. So scientists on research ships haul up buckets of sludge from the seafloor. Later, they send him small samples of what they’ve hauled up.

seafloor life
Samples of marine life from the seafloor sit in Jaspars’ lab.
Courtesy of Larry Mweetwa

Microbes living in the Arctic’s frigid waters break down their food using different tactics than do organisms on land. This process of turning food into energy for growth, activities and reproduction is called metabolism (Muh-TAA-buh-lizm). These pathways also produce chemicals called “secondary metabolites.” Those are chemicals the microbes don’t need to survive. Still, they may be useful to the microbes. One day they also might help people.

During a four-year project called PharmaSeas, scientists made thousands of extracts from those seafloor samples. Working with researchers from across Europe, Jaspars whittled that number down to about 700 “extracts of interest.” In about a dozen of them, researchers found compounds that can kill bacteria that some of today’s antibiotics cannot. Three other newfound chemicals reduce epileptic seizures (electrical storms in the brain) in mice. Yet another compound may reduce the symptoms of Alzheimer's disease. That chemical came from a previously collected sea sponge from the Philippines.

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microbe plates
Jaspars grows deep-sea microbes on plates in his lab. He’ll test the growing colonies to find out whether they make any molecules that might become new medicines.
Courtesy of Larry Mweetwa

Soon Jaspars will start the same process with new batches of mud from Antarctica. These samples were dredged up as deep as 5,000 meters (3.1 miles). The pressure at that depth is far greater than at sea level. With a new lab instrument, Jaspars will be able to simulate that pressure. That will help the microbes from the seafloor feel like they’re at home. Researchers need to recreate such harsh conditions to nurture organisms that are used to extreme habitats. And, Jaspars suspects, such organisms will likely make metabolites no one has ever seen before.

Secrets of sponges

Shirley Pomponi
Shirley Pomponi checks out a sponge. “Sponges have to filter out bacteria, viruses and all kinds of stuff from the water which might be harmful,” she says. Some of these compounds might prove useful as human drugs.
Courtesy of S. Pomponi

Unlike Jaspars, Shirley Pomponi never dreamed of becoming a deep-sea diver. She planned to be a nurse. But after her first dive, she knew there was no way she was going to spend the whole rest of her life on land.

“The freedom was amazing,” Pomponi says, recalling her early dives in the Caribbean Sea. “You’re breathing underwater — almost weightless — and looking at all these amazing things.”

Sponges fascinated her the most. These simple animals live everywhere, from shallow waters to deep seas. Because they’re always anchored to the seafloor, they can’t move if another sponge tries to overtake them. So sponges make chemicals to protect themselves against hostile invaders. Some of those defense chemicals might lead to new drugs.

For example, some sea-sponge chemicals poison an invading sponge by stopping its cells from dividing. Halting cell growth is also a key way to stop cancers, Pomponi notes. Cancers are basically cells that invade healthy tissue, where they endlessly divide, or grow.

Shirley Pomponi, Mir submersible
Pomponi stands beside Mir, a Russian submersible, just before a dive into Lake Baikal. At 1,642 meters (5,387 feet), this freshwater lake in southeastern Siberia is thought to be the world’s deepest.
Courtesy of S. Pomponi

Pomponi found one such promising chemical on one of her most memorable dives. It had been in the Caribbean. She was part of a team that discovered an anti-cancer compound being made by a deep-water sponge. The organism’s name was Discodermia dissoluta (Dis-ko-DER-mah Dis-soh-LEU-tah). Later, researchers turned the sponge compound into a drug called discodermolide (Dis-koh-DER-moh-lyde).

Since then, this biologist has made too many dives to count. More than 300 of her underwater trips were in submersibles, a type of mini-submarine. These vessels can descend to 900 meters (roughly 3,000 feet). Pomponi specializes in categorizing sponges by how closely or distantly related they are to other sponge species. That might sound boring. But a college assignment on sponge systematics — the history of naming their species — changed the course of her life.

Recalls Pomponi, “I got to play detective: Who first named this sponge? Then who changed the name? When?” The assignment was harder than she expected. She needed extra time to finish the project. “By the end, I thought sponges were totally cool. And that led to teaching myself how to identify them,” she says.

Identifying sponges is important because those from closely related families often make similar chemicals. What Pomponi learned about them led other researchers to invite her on undersea expeditions. And after many years, that led to the job she holds now. Pomponi directs the Cooperative Institute for Ocean Exploration, Research and Technology. It’s funded by the National Oceanic and Atmospheric Administration. From her base in Fort Pierce, Fla., she travels the world in search of more sponges that could yield new medicines.

Phakellia sponge
The vein-like pattern on this sponge makes it one of Pomponi’s favorites. There are more than 10,000 species of sponges. Around for more than 600 million years, she notes that some have evolved strategies for living in harsh environments.
Courtesy of Islands in the Sea 2002, NOAA/OER

As much as she loves diving and finding new sponges, Pomponi wants to limit how many sponges people remove from the sea. One way to do that is by only taking small samples — not the whole animal. “If you leave enough of a sponge and its attachment to the bottom, then it will grow back,” she explains.

She’s also working on growing sponges in the lab. By adding nutrients to just a few sponge cells, she can coax them to grow, divide and make their unusual chemicals in a flask. It’s not easy. The conditions have to be just right before those cells will divide. But if she is successful, researchers will not need to collect so many wild sponges.

That could help scientists answer even more questions. “I’m always wondering what else we can learn about sponges,” Pomponi says. For example, “Why don’t they ever get cancer?” Finding that answer might one day lead to disease treatments — or even new diets or other strategies that prevent cancer in people.

Glowing in the dark

Night is the best time to be underwater, according to biologist David Gruber. That’s when he searches for things that glow in the dark — red corals, green eels or maybe fish with shining eyes.

“Why and how do these creatures make their colors?” he wants to know. “And could those colors help humans?” 

A love of surfing spurred Gruber’s interest in ocean science. He wanted to learn everything he could about the sea. Now he’s a biologist at City University of New York and a researcher at the American Museum of Natural History in New York City.

Unlike most people, Gruber really likes to swim in the dark.

In the ocean, sunlight doesn’t reach very far beneath the sea surface. Below about 30 meters (100 feet), there is only blue light. In that blue world, some animals use biofluorescence (By-oh-flor-ESS-ens) to turn that light into greens, oranges and reds.

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fluorescent eel
A fluorescent green false moray eel (lower right corner) almost escaped Gruber’s notice during one of his dives in the Caribbean Sea.
Jim Hellemn, D.F. Gruber et al/PLOS ONE 2015

“The way animals use this glowing mechanism sounds like a science fiction story,” Gruber says. These animals use colored molecules called pigments. The pigments absorb incoming blue light, then send that light back out. The re-emitted light has less energy and a longer wavelength. It might look green, orange or red. This is different from bioluminescence (BY-oh-lew-min-ESS-ens), where animals make their own light through chemical reactions. The colors and light may help animals find each other, attract prey or hide from predators, Gruber says.

One pigment used by biofluorescent creatures is called GFP. That’s short for green fluorescent protein. Researchers have been using this molecule over the years for a range of purposes. It can highlight certain cells in tissues from a wide range of organisms. It can tag molecules during chemical reactions or to follow their movements inside cells. In one study, it was even used to tag the fur of cats that were carrying an important gene. In the dark, those cats actually glowed green.

Beyond green

But scientists wanted more colors to work with.

GFP was first discovered in jellyfish. So one of Gruber’s first missions was to find some other sea creature that would glow red. He teamed up with a neuroscientist who also liked to dive. The pair went to Australia’s Great Barrier Reef.

“We swim along looking for something with the right spectra, or range of colors,” Gruber explains.

David Gruber
“We’re completely geeked out when we swim,” Gruber says. His gear includes intense blue lights, designed to trigger a fluorescent response in the types of proteins he hopes to find. He also carries a tool that measures wavelengths of light.
Elias Carlson

He and his diving team carry special lights to spot the fluorescence. “Once we find what we’re looking for, we take a tiny sample.” Back at his lab, he then removes the DNA and searches through the organism’s genes for a color-making protein. Then he uses those genes to re-create that protein in the lab. Afterward, he can probe how it works. With luck, it just might be useful for biomedical research.

On that fateful trip to Australia, the two scientists discovered a sea anemone that made a red protein new to science. In the lab, Gruber and his research team turned that red glow into an easy-to-see test for possible cancer drugs. They tagged cancer cells with this protein. When those cells are active, they fluoresce red. If some drug stops those cells from making new proteins, there’s no glow.

During another dive trip to search coral reefs in the Bahamas, Gruber's team passed a small eel. It was glowing green. Gruber didn’t even notice the unusual eel until weeks later, when he was looking over his photos. As it turned out, that eel's glow came from an entirely new family of fluorescent proteins — ones totally different than GFP.

“Each time we find fluorescence in another animal, it’s like a whole new can of worms,” says Gruber. It can take years to figure out how what turns the color on or off.

More recently, another surprise swam past Gruber during a full-moon dive in the Solomon Islands. While his blue lights shone on a coral reef, a hawksbill sea turtle glided into the glare. For the first time, Gruber's cameras captured a green and red fluorescent pattern on the turtle’s shell. He's just beginning to decipher what kind of chemistry that turtle uses.

There’s no shortage of colorful mysteries for Gruber to solve. He also wants to understand how marine creatures might view each other. What do sea turtles really see?

“It’s like getting invited to a psychedelic party,” Gruber says. “I’m so fortunate to be a scientist who gets to put on a wetsuit and spend a lot of time in the water. I like to think about how to use our technology, not only for medicine, but to get us closer to nature.”

Power Words

(for more about Power Words, click here)

Alzheimer’s disease     An incurable brain disease that can cause confusion, mood changes and problems with memory, language, behavior and problem solving. No cause or cure is known.

Antarctica     A continent mostly covered in ice, which sits in the southernmost part of the world.

antibiotic     A germ-killing substance, usually prescribed as a medicine (or sometimes as a feed additive to promote the growth of livestock). It does not work against viruses.

Arctic     A region that falls within the Arctic Circle. The edge of that circle is defined as the northernmost point at which the sun is visible on the northern winter solstice and the southernmost point at which the midnight sun can be seen on the northern summer solstice. The high Arctic is that most northerly third of this region. It’s a region dominated by snow cover much of the year.

bacteria     (singular: bacterium) Single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside other living organisms (such as plants and animals).

biofluorescence     The light emitted from a living organism. This light is not produced by a chemical reaction within the organism. Instead, some tissue in the organism absorbs light (energy) at one wavelength (color). This chemically excites molecules in that tissue. To relax, they release that energy at a different, lower-energy wavelength.

biology     The study of living things. The scientists who study them are known as biologists.

bioluminescence     The light emitted by certain animals — such as fireflies, squid and deep-sea fishes — and by some shallow-water algae.

cancer     Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.

Caribbean     The name of a sea that runs from the Atlantic Ocean in the East to Mexico and Central American nations in the West, and from the southern coasts of Cuba, the Dominican Republic and Puerto Rico down to the northern coasts of Venezuela and Brazil. The term is also used to refer to the culture of nations that border on or are islands in the sea.

cell     The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall.

chemical     A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.

chemical reaction     A process that involves the rearrangement of the molecules or structure of a substance, as opposed to a change in physical form (as from a solid to a gas).

chemistry     The field of science that deals with the composition, structure and properties of substances and how they interact. Scientists use this knowledge to study unfamiliar substances, to reproduce large quantities of useful substances or to design and create new and useful substances. (about compounds) Chemistry also is used as a term to refer to the recipe of a compound, the way it’s produced or some of its properties. People who work in this field are known as chemists.

compound     (often used as a synonym for chemical) A compound is a substance formed when two or more chemical elements unite (bond) in fixed proportions. For example, water is a compound made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O.

coral     Marine animals that often produce a hard and stony exoskeleton and tend to live on reefs (the exoskeletons of dead ancestor corals).

current     A fluid — such as of water or air — that moves in a recognizable direction.

DNA     (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.

eel     A fish with a snake-like body and no scales. Many migrate from freshwater to salt water when it’s time to spawn.

environment     The sum of all of the things that exist around some organism or the process and the condition those things create. Environment may refer to the weather and ecosystem in which some animal lives, or, perhaps, the temperature and humidity (or even the placement of components in some electronics system or product).

epilepsy     (adj. epileptic) A neurological disorder characterized by seizures.

expedition     A journey (usually relatively long or over a great distance) that a group of people take for some defined purpose, such as to map a region’s plant life or to study the local microclimate.

extract     (v.) To separate one chemical (or component of something) from a complex mix. (noun) A substance, often in concentrated form, that has been removed from its natural source. Extracts are often taken from plants (such as spearmint or lavender), flowers and buds (such as roses and cloves), fruit (such as lemons and oranges) or seeds and nuts (such as almonds and pistachios). Such extracts, sometimes used in cooking, often have very strong scents or flavors.

flask     A type of container with a narrow neck. In the laboratory, sterile flasks made from glass are used for conducting chemical and biological experiments.

fluorescent     (v. fluoresce) Adjective for something that is capable of absorbing and reemitting light. That reemitted light is known as fluorescence.

genetic     Having to do with chromosomes, DNA and the genes contained within DNA. The field of science dealing with these biological instructions is known as genetics. People who work in this field are geneticists.

Great Barrier Reef     Some 2,300 kilometers (1,430 miles) long, this natural coral habitat is the largest living structure on Earth. In coastal waters off of northeastern Australia, It’s big enough to see from space. It’s home to some 3,000 coral reefs, 600 islands, and hundreds of types of 600 types corals, more jellyfish, mollusks, worms and fish. It’s also patrolled by more than 30 species of whales and dolphins.

Great Britain     The collective name for England, Scotland, Wales and their associated islands. This is not the same as the United Kingdom, which is the combination of Great Britain and Northern Ireland.

green fluorescent protein (or GFP)    A protein originally discovered in a jellyfish (Aequorea Victoria) that glows a bright green when illuminated with blue light. In the jellyfish, that blue light comes from the animal itself. Scientists now insert the gene to produce GFP into tissues, then use its tell-tale glow to watch where the affected genes move within the tissue or to see under what conditions cells with those genes are active.

habitat     The area or natural environment in which an animal or plant normally lives, such as a desert, coral reef or freshwater lake. A habitat can be home to thousands of different species.

marine     Having to do with the ocean world or environment.

mechanism     The steps or process by which something happens or “works.” It may be the spring that pops something from one hole into another. It could be the squeezing of the heart muscle that pumps blood throughout the body. It could be the friction (with the road and air) that slows down the speed of a coasting car. Researchers often look for the mechanism behind actions and reactions to understand how something functions.

metabolism     (adj. metabolic)  The set of life-sustaining chemical reactions that take place inside cells and bigger structures, such as organs. These reactions enable organisms to grow, reproduce, move and otherwise respond to their environments.

metabolite      Some chemical that is essential to metabolism or that is formed during the process of metabolism. See also secondary metabolite.

microbe     Short for microorganism. A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.

molecule     An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).

National Oceanic and Atmospheric Administration (or NOAA)    A science agency of the U.S. Department of Commerce. Initially established in 1807 under another name (The Survey of the Coast), this agency focuses on understanding and preserving ocean resources, including fisheries, protecting marine mammals (from seals to whales), studying the seafloor and probing the upper atmosphere.

neuroscientist     Someone who studies the structure or function of the brain and other parts of the nervous system.

nutrient     A vitamin, mineral, fat, carbohydrate or protein that a plant, animal or other organism requires as part of its food in order to survive.

organism     Any living thing, from elephants and plants to bacteria and other types of single-celled life.

pigment     A material, like the natural colorings in skin, that alter the light reflected off of an object or transmitted through it. The overall color of a pigment typically depends on which wavelengths of visible light it absorbs and which ones it reflects. For example, a red pigment tends to reflect red wavelengths of light very well and typically absorbs other colors. Pigment also is the term for chemicals that manufacturers use to tint paint.

predator     (adjective: predatory) A creature that preys on other animals for most or all of its food.

pressure     Force applied uniformly over a surface, measured as force per unit of area.

prey     (n.) Animal species eaten by others. (v.) To attack and eat another species.

protein     A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.

psychedelic     An adjective (especially popular in the 1960s) that refers to the abnormal mental experiences (such as hallucinations) brought on by use of certain drugs (such as LSD), and sometimes described as swirling, kaleidoscope-like, color patterns.

range     The full extent or distribution of something. For instance, a plant or animal’s range is the area over which it naturally exists.

reef     A ridge of rock, coral or sand. It rises up from the seafloor and may come to just above or just under the water’s surface.

risk     The chance or mathematical likelihood that some bad thing might happen. For instance, exposure to radiation poses a risk of cancer. Or the hazard — or peril — itself. (For instance: Among cancer risks that the people faced were radiation and drinking water tainted with arsenic.)

robot     A machine that can sense its environment, process information and respond with specific actions. Some robots can act without any human input, while others are guided by a human.

science fiction     A field of literary or filmed stories that take place against a backdrop of fantasy, usually based on speculations about how science and engineering will direct developments in the distant future. The plots in many of these stories focus on space travel, exaggerated changes attributed to evolution or life in (or on) alien worlds.

sea     An ocean (or region that is part of an ocean). Unlike lakes and streams, seawater — or ocean water — is salty.

secondary metabolite     Some chemicals produced by an organism during the process of metabolism that aids the organism but is not strictly essential to its  survival. Examples include germ-killing antibiotics (that may help keep some organism survive in a microbial soup without succumbing to infections). Other secondary metabolites might act as defensive weapons or even as hormones.

seizure     A sudden surge of electrical activity within the brain. Seizures are often a symptom of epilepsy and may cause dramatic spasming of muscles.

shark     A type of predatory fish that has survived in one form or another for hundreds of millions of years. Cartilage, not bone, gives its body structure.

species     A group of similar organisms capable of producing offspring that can survive and reproduce.

spectrum     (plural: spectra) A range of related things that appear in some order. (in light and energy) The range of electromagnetic radiation types; they span from gamma rays to X rays, ultraviolet light, visible light, infrared energy, microwaves and radio waves.

sponge     A primitive aquatic animal with a soft, porous body.

strategy     A thoughtful and clever plan for achieving some difficult or challenging goal.

submarine     A term for beneath the oceans. (in transportation) A ship designed to move through the oceans, totally submerged. Such ships — especially those used in research — are also known as submersibles.

systematics     The field of biology that studies evolutionary relationships among living things. People who work in this field create “family trees” that show which creatures descended from common ancestors. The same people often practice “taxonomy,” naming new species or other groupings that they identify.

tag     (in cell biology) The attachment of a chemical that stains a cell (or cell part) or that glows when a certain wavelength of light hits it. 

tissue     Made of cells, any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues.

wavelength     The distance between one peak and the next in a series of waves, or the distance between one trough and the next. Visible light — which, like all electromagnetic radiation, travels in waves — includes wavelengths between about 380 nanometers (violet) and about 740 nanometers (red). Radiation with wavelengths shorter than visible light includes gamma rays, X-rays and ultraviolet light. Longer-wavelength radiation includes infrared light, microwaves and radio waves.

NGSS: 

  • MS-PS1-1
  • MS-PS1-2
  • MS-PS1-3
  • MS-LS1-1
  • MS-LS1-2
  • MS-LS2-5
  • MS-LS4-5
  • MS-ETS1-1
  • HS-LS1-1
  • HS-LS2-2
  • HS-ETS1-1
  • HS-ETS1-2
  • HS-ETS1-3

Citation

Journal: D.F. Gruber et al. Adaptive evolution of eel fluorescent proteins from fatty acid binding proteins produces bright fluorescence in the marine environment. PLOS ONE. Vol. 10, November 11, 2015, doi: 10.1371/journal.pone.0140972.