Mud and sponges probably aren’t high on most divers’ bucket lists. But scientist and explorer Professor Brian Murphy, based at the University of Illinois at Chicago, has his sights set on the sediments that lurk at the bottom of lakes and the gooey animals that cling to sunken shipwrecks. And for good reason. When he brought a blob of mud from Lake Michigan, he found that it contained bacteria that create two previously unknown molecules.
Lab tests showed that this class of compounds is lethal to the bacteria that causes tuberculosis, a disease that existing drugs struggle with. “For millions of years, bacteria have been fighting each other,” Murphy says. “We’re just harnessing that power.”
Superbugs are on the rise all over the world. In recent years there have been a number of patients with strains of E coli that are resistant to many antibiotics, including drugs that doctors only use as a last resort. It is an alarming trend in which bacteria are gaining the upper hand in their battle against the antibiotics we use to kill them, accelerated by the overuse of these drugs in the world.
“The way to fight drug resistance is to find new chemistry,” Murphy says. He is one of many modern day prospectors looking for that new underwater chemistry.
Medicines from the deep
From icy polar seas to scorching hydrothermal vents, and from coral reefs to inland lakes, the vast wetlands that cover seven-tenths of our planet are home to an immense diversity of life. They include many animals that developed complex chemical defense mechanisms, along with an abundance of microbes; about 90 percent of ocean life is thought to be microscopic. Among these creatures, researchers are discovering molecules that could form the basis for new drugs.
Tapping into the natural world for medicines is nothing new – throw an aspirin and your headache will be soothed by a compound discovered in willow bark. With the emerging wave of drug resistance, the hope is that nature has a lot more in her medicine cabinet for us to dive into. The trick is to sort through all those powerful chemicals to find the ones that can fight disease.
“It’s no secret that there is an incredibly high failure rate in drug development,” Murphy says. “It’s really hard to find a set of molecules that can target a specific disease and do so within the incredibly complex environment of the human body.”
To help with this, Murphy is working to make the sample collection process smarter, as this is one of the few drug development steps that hasn’t seen a major revolution in recent decades. According to Murphy, looking for molecules in original places is an important part of drug development, so he decided to use an entirely new resource: the general public.
Talking to recreational divers gave Murphy the idea to search for sponges in shipwrecks. These unattractive animals spend most of their lives in place, straining the water for food and taking in hordes of bacteria. “Bacteria can make up as much as 30 or 40 percent of sponge biomass,” explains Murphy.
Freshwater sponges are common in the Great Lakes of the US, but almost nothing is known about them. Instead of going out and collecting sponges himself – a time-consuming and expensive business – Murphy led a citizen science project in which he asked divers to collect small samples for him. while they are outside. He sent out collection kits and got a great response, receiving over 40 clumps of sponge in the mail.
In 2016, he rolled out the project across the Great Lakes and hopes to test as many locations as possible. Ultimately, Murphy wants to map the spread of sponges and bacteria across the lakes so that future efforts can be more effective and land in fertile spots both in the Great Lakes and beyond.
Read more about the ocean:
These creatures contain chemicals that can beat cancer, MRSA and more
- Horseshoe Crabs: The blood of these arthropods is full of amoebocyte cells that respond to tiny spores of bacteria. Their blood has been used to test equipment and vaccines for contamination for the past 50 years.
- Cone snails: The stings of these mollusks 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.
- Puffer fish: These fish contain tetrodotoxin (or TTX). This is what makes fugu (a delicacy made from puffer fish) a risky dinner. TTX is being developed as a treatment for the pain suffered during chemotherapy.
- Micrococcus luteus† This bacterium produces a pigment called sarcinaxanthin that can block long-wavelength UV radiation. This could be used in the development of more effective sunscreens.
- Dendrila membranosa† This sea sponge contains a molecule called darwinolide. This substance has been shown to be effective against the resistant MRSA superbug, which can often cause problems in hospitals.
- Elysia rufescens† This species of sea snail has a wide distribution. It contains a substance called kahalalide F, which is currently under investigation as a potential anti-tumour agent.
Scientists search the deepest parts of the ocean
When bioprospectors first turned to the oceans in the 1950s, their first targets were coral reefs. These bustling ecosystems, teeming with species, are a logical place to look, and they have yielded many natural products, including some that have reached the end of the drug development pipeline.
Early on was the chemotherapy drug cytarabine, approved in the US in 1969 and originally found in a sponge on a Florida Keys reef. Another cancer-fighting drug called trabectedin, which comes from a Caribbean sea pipe, has been used in Europe since 2007 and in the US since 2015.
Elsewhere, other researchers are chasing even further beneath the waves for new chemistry. An international team called PharmaSea, led by Prof. Marcel Jaspars, is looking for new antibiotics in the deep sea, including at the bottom of trenches – the deepest parts of the oceans. Jaspars describes these as “negative islands” that protrude into the seafloor, rather than pointing upward. “It is possible that there 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 return mud full of unique bacteria. Techniques to keep these extreme creatures alive in the lab have advanced in recent years, so experiments can be conducted. According to Jaspars, they have done about 100,000 tests, including the so-called ESKAPE pathogens. This group of six bacterial strains shows a growing resistance to several existing antibiotics.
Ultimately, the PharmaSea team aims to refine two compounds that can be produced on a larger scale and proposed for preclinical trials. So far their most promising finds are compounds that could be effective against diseases of the nervous system, especially epilepsy and Alzheimer’s disease.
Who will benefit?
But whose are these discoveries from the deep? The word “bio-prospecting” usually has a negative connotation. At worst, it is reminiscent of indigenous people who give away their knowledge of traditional medicines and receive little compensation.
Fortunately, things have moved on in recent years and benefit-sharing protocols are now commonplace. Prior to collecting, researchers usually make written agreements with the country of origin. In 2010, the international Nagoya Protocol came into force, making such agreements a legal requirement. But not everyone is signed up to Nagoya – the US is noticeably absent.
The ‘high seas’ start 200 nautical miles offshore and technically belong to no one, making them difficult to control. Currently, the United Nations Convention on the Law of the Sea (UNCLOS) includes certain activities, including deep-sea mining and cable laying, but it says nothing about biodiversity. In 2020, formal discussions have begun to change UNCLOS to bioprospect. There are different points of view at the negotiating table. “The G77 and China believe that this should be the common heritage of humanity, meaning that everyone could benefit from it,” explains Jaspars. The idea is that a single country or company should not benefit alone.
On the other hand, there is the concept of ‘Freedom of the High Seas’, backed by the US and Norway, which would give any nation the freedom to bio-prospect on the high seas, just like anyone can fish there. They could research anywhere and keep the profits. Other groups, including the EU, are eager to find a solution. It will probably be several more years before bio-prospecting on the high seas is regulated.
The next steps
Back in the lab, Murphy’s tuberculosis-fighting molecules enter the next round of testing to see if they could lead to new drugs. Even if they don’t, Murphy is confident they will still be useful. “They showed very selective antibacterial activity against tuberculosis,” he says. Other bacteria were left untouched. Figuring 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.
But bio-seekers will have to hurry. In recent years, the ailing 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 irreversibly sick.
Read more about antibiotics†