Underwater Pharmacy: Meet the Scientists Raiding the Ocean’s Medicine Cabinet

Mud and sponges probably aren’t high on most divers’ wish lists. But scientist and explorer Professor Brian Murphy, based at the University of Illinois at Chicago, has his sights set on sediment lurking at the bottom of lakes and gooey animals clinging to submerged shipwrecks. And for good reason. When he brought back a drop of mud from Lake Michigan, he discovered that it contained bacteria that create two previously unknown molecules.

Laboratory tests have shown that this class of compounds is lethal to the bacteria that cause tuberculosis, a disease that existing drugs fight. “For millions of years, bacteria have been fighting each other,” says Murphy. “We’re just harnessing that power.”

Around the world, superbugs are on the rise. There have been a number of patients in recent years who have strains of E. coli that are resistant to many antibiotics, including drugs that doctors use only as a last resort. It’s an alarming trend where bacteria are gaining ground in their battle against the antibiotics we use to kill them, accelerated by the world’s overuse of these drugs.

“The way to combat drug resistance is to find a new chemical,” says Murphy. He’s one of many prospectors today looking for that new underwater chemistry.

medicine of the deep

From icy polar seas to scorching hydrothermal vents, and from coral reefs to inland lakes, the vast aquatic realms that cover seven tenths of our planet are home to an immense diversity of life. They include many animals that evolved complex chemical defenses, along with a profusion of microbes; About 90 percent of ocean life is thought to be microscopic. From among these creatures, researchers are discovering molecules that could form the basis of new drugs.

Brian Murphy watches as his graduate student, Michael Mullowney, jumps into the water near Iceland’s Grimsey Island, home to one of the world’s largest puffin colonies. Scientists from the University of Illinois at Chicago traveled to Iceland in May 2014 to search for new antibiotics underwater. © Jennifer Yang/Toronto Star via Getty Images

Harnessing the natural world for pharmaceuticals is nothing new: Take an aspirin and your headache will be relieved by a substance discovered in willow bark. With the rising tide of drug resistance, the hope is that nature has plenty more in its medicine cabinet for us to dive into. The trick is to sift through all those potent chemicals to find the ones that might fight disease.

“It’s no secret that there is an incredibly high failure rate in drug development,” says Murphy. “It’s really hard to find a set of molecules that can attack a specific disease and do it within the incredibly complex environment of the human body.”

To help with this, Murphy is working to improve the sample collection process, as it is one of the few steps in drug development that has not undergone a major revolution in recent decades. According to Murphy, looking for molecules in the original places is an important part of drug development, so he decided to use an entirely new resource: the general public.

A diver descends during a technical dive in the Great Lakes. Great Lakes, United States of America © Luis Lamar/National Geographic/Getty Images

Talking to recreational divers gave Murphy the idea to look for sponges in shipwrecks. These unattractive animals spend most of their lives stuck in one place, sifting through the water for food and battling hordes of bacteria. “Bacteria can make up as much as 30 to 40 percent of the biomass in sponges,” explains Murphy.

Freshwater sponges are common in the US Great Lakes, but almost nothing is known about them. Rather than go out and collect sponges himself, an expensive and time-consuming business, Murphy led a citizen science project asking divers to collect tiny samples for him. while they are away from home. She sent out collection kits and got a great response, receiving over 40 sponge balls in the mail.

In 2016, he launched the project across the Great Lakes and hopes to test as many sites as possible. Ultimately, Murphy wants to map the distribution of sponges and bacteria in the lakes so that future efforts can be more effective and target fruitful locations, both in the Great Lakes and beyond.

Read more about the ocean:

These Critters Contain Chemicals That Could Beat Cancer, MRSA, and More

  • Horseshoe crabs: The blood of these arthropods is full of amebocyte cells that react to small traces of bacteria. His blood has been used for the last 50 years to test equipment and vaccines for contamination.
  • Cone snails: The bites of these molluscs contain conotoxins. There is already a conotoxin-based pain reliever that is more potent than morphine. There are also treatments for cancer and diabetes on the horizon.
  • spiny starfish: The body of this starfish is covered in slime that consists of 14 percent carbohydrates and 86 percent protein. The substance is being investigated as a treatment for arthritis and asthma.
  • Blowfish: These fish contain tetrodotoxin (or TTX). This is what makes fugu (a delicacy made from puffer fish) such a risky dinner. TTX is being developed as a treatment for pain experienced during chemotherapy.
  • Micrococcus luteus: This bacterium produces a pigment called sarcinaxanthin that can block long-wave ultraviolet radiation. This could be used in the development of more effective sunscreens.
  • membranous dendrill: This sea sponge contains a molecule called darwinolide. This substance has been found to be effective against the drug-resistant superbug MRSA, which can often cause problems in hospitals.
  • Elysia rufescens: This species of sea slug has a wide distribution. It contains a substance called kahalalide F, which is currently being investigated as a potential tumor-fighting agent.

Scientists are looking in the deepest parts of the ocean

When bioprospectors first turned to the oceans in the 1950s, their initial targets were coral reefs. These bustling ecosystems, teeming with species, are a logical place to look and have produced many natural products, including some that made it to the end of the drug development pipeline.

At first it was the chemotherapy agent cytarabine, approved in the US in 1969 and originally found in a sponge on a reef in the Florida Keys. Another anticancer agent called trabectedin, from a Caribbean sea squirt, has been used in Europe since 2007 and in the US since 2015.

Some sea squirts contain cancer-fighting agents © FLPA

Elsewhere, other researchers are searching even further beneath the waves for novel chemistry. An international team called PharmaSea, led by Professor Marcel Jaspars, is searching for new antibiotics in the deep sea, including at the bottom of trenches, the deepest parts of the oceans. Jaspars describes them as “negative islands” that reach down into the seabed, rather than pointing up. “There may have been millions of years of separate evolution in each trench,” he says.

Jaspars and his collaborators send unmanned probes miles into the depths to bring up mud loaded with unique bacteria. Techniques for keeping these extreme creatures alive in the laboratory have advanced in recent years, so experiments can be carried out. According to Jaspars, they have performed around 100,000 tests, with targets including so-called ESKAPE pathogens. This group of six bacterial strains is showing increasing resistance to multiple existing antibiotics.

PharmaSea researchers exploring ocean mud © MJ Press

Ultimately, the PharmaSea team aims to narrow down two compounds that can be produced on a larger scale and submitted for preclinical trials. Their most promising findings so far are compounds that could be effective against diseases of the nervous system, particularly epilepsy and Alzheimer’s disease.

Who will benefit?

But who owns these discoveries from the deep? The word ‘bioprospecting’ often has a negative connotation. At worst, it reminds indigenous peoples of giving away their traditional medicine knowledge and receiving little reimbursement.

Fortunately, things have moved on in recent years and profit-sharing protocols are now commonplace. Before collecting anything, researchers usually sign written agreements with the country of origin. In 2010, the international Nagoya Protocol entered into force, making such agreements a legal requirement. But not all are enrolled in Nagoya: the United States is conspicuously absent.

The ‘high seas’ begin 200 nautical miles from shore and technically belong to no one, making it difficult to monitor. Currently, the United Nations Convention on the Law of the Sea (UNCLOS) covers certain activities, including deep sea mining and cable laying, but is silent on biodiversity. Formal discussions began in 2020 to amend UNCLOS to cover bioprospecting. Several opinions are on the negotiating table. “The G77 and China believe that it should be the Common Heritage of Humanity, which would mean that everyone could benefit,” explains Jaspars. The idea is that no single nation or company should be allowed to benefit solely.

On the other hand, there is the ‘Freedom of the High Seas’ concept, backed by the US and Norway, which would give any nation the freedom to bio-prospect the high seas, just as anyone can fish there. They could investigate anywhere and keep the profits. Other groups, including the EU, are eager to find a solution. It is likely that it will take several years for bioprospecting on the high seas to be regulated.

The following steps

Back in the lab, Murphy’s anti-TB molecules are entering the next round of testing to see if they can lead to new drugs. Even if they don’t, Murphy is confident they’ll still be useful. “They showed very selective antibacterial activity toward tuberculosis,” he says. Other bacteria remained intact. Finding out exactly how these molecules selectively kill the tuberculosis bacteria could reveal vital information about the disease itself and perhaps point the way to effective drugs.

Aerial shot of the Great Barrier Reef in the Whitsundays Australia © Getty Images

But bioprospectors will have to hurry. In recent years, the deteriorating Great Barrier Reef has made headlines around the world, and human activities continue to threaten the health and biodiversity of the Earth’s oceans, rivers, and lakes. Let’s hope we can find the medicines and cures we need before the waters of our planet become irrevocably sick.

Read more about antibiotics:

Underwater Pharmacy: Meet the Scientists Raiding the Ocean’s Medicine Cabinet

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