The ocean floor is full of secrets, but scientists recently discovered one of its best-kept secrets. For 25 years, drug hunters have been searching for the source of a natural chemical that has shown promising results in early cancer treatment studies. Now, researchers at the University of Utah Health report that easy-to-find soft corals — resilient corals that resemble underwater plants — are the elusive compound.
Pinpointing the source allowed the researchers to dig deeper and find the animal’s DNA code for the chemical’s synthesis. By following these instructions, they were able to perform the first steps in recreating the chemical soft coral in the laboratory.
“This is the first time we’ve been able to do this with a drug in mind on Earth,” said Eric Schmidt, PhD, professor of medicinal chemistry at U of U Health. He led the study with Paul Scesa, PhD, postdoctoral scientist and first author, and Zhenjian Lin, PhD, research assistant professor.
This breakthrough opens the possibility of mass-producing the compound needed for rigorous testing and could one day lead to a new tool in the fight against cancer.
A second research group led by Bradley Moore, PhD, of the Scripps Institution of Oceanography at the University of California, San Diego, independently demonstrated that corals make connected molecules. Both studies were published in the May 23 issue of natural chemistry biology.
A world of possibilities
Soft corals contain thousands of drug-like compounds that can act as anti-inflammatory agents, antibiotics, etc. But getting enough of these compounds has been a major obstacle to developing them into drugs for clinical use. These other compounds should now also be accessed using this new approach, Schmidt says.
Corals aren’t the only animals harboring potential cures. Nature is teeming with snakes, spiders, and other animals that are known to carry chemicals with healing properties. However, these soft coral compounds provide distinct advantages for drug development, Schmidt says.
Unlike toxic chemicals that are injected into prey, corals use their own chemicals to fend off predators that try to eat it. Because they are made to be eaten, the chemicals in soft corals are easy to digest. Likewise, medicines derived from these types of compounds should be able to be taken as tablets with a glass of water, and not by injection or other more invasive means. “These compounds are hard to find, but it’s easier to make in the lab and easier to take as medicine,” Schmidt says.
These possibilities have simply been out of reach for decades. Getting to that point literally takes a bit of luck.
Find the source
Scesa found the long-awaited compound in a common type of soft corals that lives off the coast of Florida, just a mile from his brother’s apartment. In the 1990s, marine scientists reported that a rare coral near Australia carried a chemical, erythropin, that had anti-carcinogenic properties. The chemical disrupts the cytoskeleton, a mainstay in cells, and soft corals use as a defense against predators. But lab studies have shown that the compound is a powerful inhibitor of cancer cell growth as well.
In the decades that followed, scientists searched but could not find the legendary “holy grail” chemical in the quantities needed for drug development and could not solve the problem without understanding how the chemical was made. The doctrine says that, like other types of marine life, the chemical was synthesized by symbiotic organisms that live inside the animals.
“It didn’t make any sense,” Sesa said. “We knew that corals must produce erythropin. After all, he and Schmidt concluded that some types of soft corals do not have symbiotic organisms and yet their bodies contain the same class of chemicals.”
Solving the puzzle seemed like work done for Scesa. As a kid growing up in Florida, the ocean was his playground and he spent countless hours exploring its depths and wildlife. In graduate school, he developed a fondness for organic chemistry and combined the two interests to better understand the chemical diversity of the seas.
Later, he joins the natural products scientist Schmidt’s laboratory on a mission to track down the main source of the drug. Sessa suspected that his familiar coral species might have the answer and brought small live specimens from Florida to Utah, and the real fishing began.
Decode the recipe
The next step was to see if the genetic code of the corals contained instructions for making the compound. Recent advances in DNA technology have made it possible to quickly piece together the code of any species. The difficulty was that scientists did not know what the instructions for making the chemical should look like. Imagine you’re looking for a specific recipe in a cookbook, but you don’t know the meaning of the words inside the book.
“It’s like going into the dark and looking for an answer where you don’t know the question,” Schmidt notes.
They solved the problem by finding regions of corals’ DNA that looked like genetic instructions for similar types of compounds from other species. After programming the lab-grown bacteria to follow the instructions of the soft corals’ DNA, the microorganisms were able to replicate the first steps in making a potentially curative cancer.
This proved that soft corals are the source of erythropin. He also showed that the compound could be made in the lab. Their work now focuses on filling in the missing steps in the compound’s prescription and on how best to mass-produce the potential drug.
“I hope to deliver them to the doctor one day,” Skisa says. “I think it goes from the bottom of the ocean to the seat by the bed.”
The research was supported by the National Institutes of Health and the ALSAM Foundation and published in natural chemistry biology As ‘ancient defense gene clusters of biosynthetic terpenes in soft corals’
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