Hard ocean corals, as any unfortunate surfer learns, protect themselves with their sharp rigid skeletons. But soft corals, squishy and vulnerable, are believed to use chemical defenses — including a compound that showed potential as an anti-cancer drug as long as 25 years ago.
Research has been impeded, however, by the tiny quantities that can be obtained from samples of ocean coral.
Now University of Utah researchers have discovered a way to boost production of the compound, called eleutherobin, so that it may finally make it to clinical trials.
In early experiments, eleutherobin has shown to be “really good at killing cancer cells, including cancer cells that are resistant to chemotherapy,” said Paul Scesa, a post-doctoral researcher at the U.
Eric Schmidt, a marine natural products researcher at the U., oversaw a study of the new technique published last month in the journal Nature Chemical Biology. Natural products research looks for new potential drugs in nature — think of the development of aspirin from willow bark, as a historical example.
The coral that produces eleutherobin isn’t the rocky, colorful kind that’s being bleached in threatened reefs around the world. But these soft corals also are at risk from climate change and human pollution, along with other ocean inhabitants.
“I would wager that most people have not even heard of most of the groups of animals that are found in the ocean, Schmidt said. Of those millions of species, “some of them have the potential to be transformative therapeutics,” he said, so preserving those animals and habitats is “crucially important.”
Coral in the desert
When Schmidt started out in the field of marine natural products, researchers would have to obtain animals such as corals and “grind them up” to find and use interesting compounds within.
Now researchers can use genetic analysis — taking small samples of coral to analyze their chemistry and obtain their genetic code, and figure out how they produce certain compounds, Schmidt said. That allows scientists to “be pretty non-disruptive” to the local ecosystem, he said.
The project in Schmidt’s lab began when Scesa wanted to study a type of coral from his home state of Florida.
Although Utah isn’t known for its marine life, Scesa came to the U. to do marine-related research because “Eric’s lab is one of the few in the world with the tools to do this kind of work,” Scesa said. “Even though it’s very far from the ocean and makes field work hard… I knew it was the one place where I would have the resources to solve the problem.”
Scientists think soft corals protect themselves through chemical defenses — certain compounds called terpenes, which act as deterrents and warn potential predators against trying to eat them.
Eleutherobin is an example of a terpene, a class of compounds that often happen to function as drugs in the human body, as is cannabidiol (CBD). Menthol and the distinctive smell after it rains are also terpene-based, Schmidt said.
When eleutherobin is taken from coral, refined and modified, it kills cancer cells with a mechanism similar to Taxol and its generic form, paclitaxel, which are used to treat breast cancer and other diseases.
Once team members in Schmidt’s lab figured out which genes in the coral told it to make eleutherobin, they implanted those genetic instructions into a microbe, which produces it without any more coral required.
This is an example of the field of synthetic biology, where scientists can modify living organisms to act in ways that they wouldn’t normally behave.
For any animal-created compound of interest, the microbe uses the animal’s genetic code to make proteins and the team purifies and transforms those proteins into the compounds they desire, Schmidt said.
Solving a long-standing mystery
The question of how these chemicals appeared in corals was a mystery for decades, said Bradley Moore, a chemical biologist at the Scripps Institution of Oceanography at the University of California San Diego.
Scientists had only expected complex chemicals to form in plants and microbes, he explained.
Though the chemicals appeared across all kinds of plants, it took genetic methods to finally prove that, surprisingly, it was the animals themselves that were making the defense chemicals, instead of a symbiotic microbe.
This is the first time this class of chemicals has been found in animals, Moore said.
His lab published a closely related study on corals in the same journal last month. “These coral-based chemicals, although they showed a lot of promise in biomedicine, have languished because of a supply issue,” Moore said.
Schmidt’s work is a “fantastic” study and helps address the supply problem, he said.
Moore’s group also studies how ocean organisms produce chemicals that could be useful for human health, though that team took a broader approach, sequencing nine different coral types.
The new findings appear extra solid because “two separate labs, both of which are very highly respected, found the same thing at the same time,” and happened to publish them in the same journal, said Katherine Maloney, a natural products researcher at Point Loma Nazarene University in San Diego, Calif. She has also studied corals but wasn’t involved with either study.
There’s still a lot of work to do to make a sufficient quantity of eleutherobin for further testing, Scesa said.
And continued study and preservation of animals around us are particularly important for humans, Schmidt said, because “about half of drugs that are currently used in the clinic, ultimately originate in natural products.”
Humans can easily wipe out an entire species in a day, he said, and completely miss out on everything it could have offered.
Correction: 5 p.m., July 8, 2022: This story has been updated to correctly describe where chemical biologist Bradley Moore works.
Leto Sapunar is a Report for America corps member covering business accountability and sustainability for The Salt Lake Tribune. Your donation to match our RFA grant helps keep him writing stories like this one; please consider making a tax-deductible gift of any amount today by clicking here.