Antarctic Expeditions Turn Up New Compounds to Fight Tropical Diseases
TAMPA, Fla. (Dec. 7, 2009) – The Antarctic is literally the last place anyone might expect to look for a treatment for a tropical disease like malaria, but under a retreating glacier is exactly where University of South Florida researchers have found the newest, promising compound that works against the devastating sickness.
That’s where USF chemist Bill Baker found a bright red sea sponge near the U.S. Antarctic Program’s Palmer Station during an expedition to Antarctica.
Working in conjunction with tropical disease expert Dennis Kyle in USF’s Department of Global Health, compounds from the sponge were tested and have been found to be active against both malaria and leishmaniasis, a parasitic disease spread by sandflies which causes skin infections. Leishmaniasis is of particular concern to U.S. troops serving in the Middle East, but also is prevalent in places like India, Bangladesh, Brazil and Sudan.
“Natural products are where drug discovery began,” said Baker, who has made a dozen trips to Antarctica in search of compounds that can cure diseases, including cancers. “This has been going on for over a century and much of the proverbial low-hanging fruit has been picked. Everything in your backyard has been studied. You have to go out to where the biodiversity is rich.”
Their findings on the sponge compounds effects on leishmaniasis was recently published in the Journal of Natural Products, the first study published from the collaboration of the two internationally-leading scientists. Of the 70,000 individual organisms extracted from the vast collection of Antarctic and other life Baker and his colleagues will study, Kyle expects at least 50 different novel compounds will be identified as potential disease fighters.
For more than two decades, Baker has scoured the world’s oceans in search of new organisms that might produce biopharmaceuticals before coming to USF in 2001. Kyle arrived at the university in 2006 following his groundbreaking work at the Infectious Disease Research Program at Walter Reed Army Institute of Research.
Their search focuses on the compounds produced in the natural world – the plants, fungi and microbes that may act against some of the world’s most fearsome diseases. Infusing new, faster technology and procedures - such as nuclear magnetic resonance spectroscopy and mass spectrometry studies - the collaboration holds the promise of taping the vast and unknown potential of marine environments.
“It’s sort of a process where you are searching for a needle in a haystack,” Kyle said. “Bill and his students go out and find the part of the haystack that’s active.”
The discovery of a new compound from the Antarctic comes at a time when scientists are trying to grapple with the problem of drug-resistant parasites. Tropical disease experts are particularly alarmed at growing evidence of that the parasite that causes malaria - Plasmodium falciparum – is becoming resistant to artemisinin, the most effective drug currently used to combat malaria.
If resistance to artemisinin drugs spreads, it will be a global disaster, Kyle said.
The benefits of any newly discovered drug are substantial. A child dies of malaria every 30 seconds – and some one million people succumb to the disease each year. Leishmaniasis causes nearly 60,000 deaths each year, leaving those who survive it with disfigured or with related health issues.
But if compounds can be gathered from far-flung parts of the world where those parasites would have had no exposure to them and thus no resistance, the opportunities for creating medicines that work more effectively and for longer periods of time increase, Baker and Kyle said.
Scientists are particularly interested in polar compounds since just three percent of the marine natural products have been culled from polar organisms and it remains an untapped source of potential medicines.
In the case of the Crella sponge – it was selected because “we take a broad approach to Antarctica and collect everything we can get our hands on,” Baker noted – it was found in a part of Antarctica called Norsel Point which was made accessible to researchers by the melting Marr Glacier. The sponge has since been found on other sites near Palmer Station, growing at depths of more than 30-meters and harvested by divers who scrapped it from the deep rock walls.
The sponge was freeze-dried and once back at Baker’s laboratory in Tampa underwent a multi-step process to extract its chemistry so it could be examined, cataloged and then tested against disease in Kyle’s lab.
There, human red blood cells infected with parasites that cause malaria and leishmaniasis were treated with the compounds. Five new steroids, called norselic acids, that were isolated from the sponges were found to be active against the parasites.
A further benefit of the discovery is that the researchers don’t need to go back to harvest more sponges to create an effective medicine, the researchers explained. Once they zero in on the chemicals which are active against the parasites, the chemicals can be recreated in the lab.
The next step, Kyle said, is to continue testing the compounds in animal models and continuing to search through the Antarctic collection for more promising chemicals, testing those against the assays in Kyle’s lab to see which ones have an effect on disease.
“The nice thing is that it’s easy to throw out a lot of it quickly because of the assays we have constructed,” Kyle said. “It helps you focus on the ones that have the most potential.”
The scientists, however, still have a long road to travel before they know whether their discovery will lead to new medicines. Drug companies typically take at least a decade to develop new medicines after the initial effective compounds are discovered, Kyle noted.
But this discovery is progress nonetheless, they note.
“One of the problems we have for these diseases is we don’t have a lot of new leads to try to develop,” Kyle said. “What we are hoping to give this community and ourselves is a whole bunch of new leads.”
The University of South Florida is one of the nation's top 63 public research universities and one of only 25 public research universities nationwide with very high research activity that is designated as community engaged by the Carnegie Foundation for the Advancement of Teaching. USF was awarded $380.4 million in research contracts and grants in FY 2008/2009. The university offers 232 degree programs at the undergraduate, graduate, specialist and doctoral levels, including the doctor of medicine. The USF System has a $1.8 billion annual budget, an annual economic impact of $3.2 billion, and serves more than 47,000 students on institutions/campuses in Tampa, St. Petersburg, Sarasota-Manatee and Lakeland. USF is a member of the Big East Athletic Conference.