A lot is going on under the ocean that we don't know yet.
Recently, scientists from the Max Planck Institute for Marine Microbiology in Bremen, Germany, found that seagrass ecosystems hold reserves of sugar we never knew existed before. And now, researchers at the University of Utah have made a breakthrough discovery - easy-to-find soft corals make the elusive compound that could possibly treat cancer!
For 25 years, drug hunters have been searching for the source of a natural chemical that had shown promise in initial studies for treating cancer.
Upon identifying the source, the researchers found the animal's DNA code for synthesizing the chemical. They were then able to recreate the soft coral chemical in the laboratory.
“This is the first time we have been able to do this with any drug lead on Earth,” says Eric Schmidt, Ph.D., professor of medicinal chemistry at U of U Health. He led the study with postdoctoral scientist and first author Paul Scesa, Ph.D., and associate research professor Zhenjian Lin, Ph.D.
Producing the long-sought-after compound in large amounts needed for rigorous testing could someday result in a new tool to battle cancer.
A second research group led by Bradley Moore, Ph.D., from the Scripps Institute of Oceanography at the University of California, San Diego, independently showed that corals make related molecules. Both studies were published today in Nature Chemical Biology.
The "holy grail"
Soft corals are known to have thousands of drug-like compounds that could double up as anti-inflammatory agents and antibiotics. But getting enough of these compounds has been a hindrance to developing them into drugs for clinical use.
Though plenty of animals such as snakes and spiders carry chemicals with healing properties, soft corals offer unique advantages.
They utilize their chemicals to primarily ward off predators that try to eat them, unlike venomous chemicals that are injected into prey. As a result, they're easily digestible. Drugs obtained from such compounds can be given as pills with a glass of water, rather than being taken by injection or other invasive means.
“These compounds are harder to find but they’re easier to make in the lab and easier to take as medicine,” says Schmidt.
The hardest task: Finding the chemical
In the 1990s, marine scientists reported that a rare coral near Australia carried eleutherobin, a chemical with anti-cancer properties. The chemical disrupts the cytoskeleton, a key scaffold in cells, and soft corals use it as a defense against predators. But laboratory studies showed that the compound was also a potent inhibitor of cancer cell growth.
Scientists searched for the fabled "holy grail" for decades after, but couldn't find the chemical in the quantities needed for drug development. Without understanding how the chemical was made, they couldn't remedy the problem.
“It didn’t make sense,” says Scesa, who studies the potential of chemicals made by soft corals as drug leads. “We knew that corals must make eleutherobin.” He and Schmidt reasoned that some soft coral species don’t have symbiotic organisms and yet their bodies contained the same class of chemicals.
It was indeed a mystery. But Scesa seemed to be the right person to solve the same.
Growing up in Florida, he spent several hours exploring the depths and wildlife of the ocean. In graduate school, he combined organic chemistry and his love for the ocean to understand the chemical diversity of the seas.
Eventually, he joined the lab of natural products scientist Schmidt with a mission to track down the source of the drug lead. Scesa had an inkling that coral species familiar to him might have the answer and brought small live samples from Florida to Utah, to begin the hunt.
He then found the compound in a common species of soft coral living off the Florida coast—just a mile from his brother’s apartment.
"Bench to bedside": If successful, the tool could save several lives
Though advances in DNA technology had made it possible to quickly piece together the code of any species, the scientists didn't know what the instructions for making the chemical must look like. Their next step was to find out if the coral's genetic code contained a directive for making the compound.
“It’s like going into the dark and looking for an answer where you don’t know the question,” says Schmidt.
They tackled the problem by finding regions of coral DNA that resembled genetic instructions for similar types of compounds from other species. Bacteria grown in the lab were programmed to follow DNA instructions specific to the soft coral. The microorganisms were then able to replicate the first steps of making potential cancer therapeutic.
While this proved that soft corals are the source of eleutherobin, it also demonstrated that the compound could be manufactured in the lab.
The scientists are now focusing on filling in the missing steps of the compound’s recipe and finding the best way to produce large amounts of the potential drug.
“My hope is to one day hand these to a doctor,” says Scesa. “I think of it as going from the bottom of the ocean to bench to bedside.”