From pit vipers to funnel web spiders, living creatures continue to prove a rich source of medicines with life-saving potential, but some are more forthcoming than others with their powerful compounds and molecules. A 25-year search for another source of a promising anti-cancer chemical produced by a rare coral species has now started to bear fruit, with the discovery other readily available corals produce the chemical in abundance.
The compound at the center of this research goes by the name of eleutherobin, and after it was isolated from a rare coral species off the coast of Australia in the 1990s, studies soon began to document its "extremely potent" and "highly cytotoxic" anti-cancer potential. Though these early results were highly encouraging, scientists were unable to find the chemical in meaningful amounts, and the lack of supply halted their ambitions for further research and drug development.
Paul Scesa, a postdoctoral scientist at the University of Utah, grew up exploring the ocean waters surrounding Florida. His studies in organic chemistry led him to wonder whether the soft coral species he'd come to know might offer some clues in this long-running search for eleutherobin, so he began lab studies of living samples sourced from the area.
Knowing that corals can produce eleutherobin is one thing, but understanding how they do it was what the scientists would really like to know. Advanced DNA technology makes it possible to study the corals' genetic code and see if it contains instructions to create the compound, but without knowing what those instructions look like exactly, the scientists faced a tricky task.
“It’s like going into the dark and looking for an answer where you don’t know the question,” said Eric Schmidt, who co-led the study with Scesa.
To fill in the blanks, the scientists applied these DNA tools to other coral species, on the lookout for genetic instructions for the creation of compounds known to be similar to eleutherobin. This enabled them to identify DNA regions in the soft coral collected by Scesa that carried a resemblance to genetic instructions other species use to produce similar types of compounds, and piece together an instruction manual of sorts for the creation of eleutherobin.
The scientists then grew bacteria in the lab and programmed it to follow these instructions, which indeed saw the microorganisms carry out the steps to create precursors for eleutherobin. According to the scientists this proved the soft corals, from which the genetic instructions were sourced, are producers of the promising anti-cancer compound. Recreating it in the lab using the creature's DNA code now raises the possibility of producing the compound in amounts needed for further research and drug development.
“This is the first time we have been able to do this with any drug lead on Earth,” said Schmidt.
Eleutherobin is a chemical used by corals to stave off would-be predators, and as such is made to be eaten, unlike venomous chemicals from snakes for example, which are injected into prey. This means that compounds based off the chemical should also be easily digestible, and could even take the form of pills that can be consumed orally with a glass of water, according to the scientists.
“These compounds are harder to find but they’re easier to make in the lab and easier to take as medicine,” says Schmidt.
The scientists are now working on the best ways to scale up production of the compound, with the hope of eventually delivering a highly potent, easily-administered treatment for cancer.
“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.”
The research was published in the journal Nature Chemical Biology.
Source: University of Utah
