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James McClintock, Ph.D.
Mission Co-Investigator

A Tunicate Anti-Cancer Discovery

Journal By J McClintock

Posted On 3/30/2004 5:28:44 AM

As our research team continues its ongoing studies of the chemical ecology of Antarctic marine macroalgae and invertebrates we take pride in the applied overtones of our basic ecological research. With pipe lines to the UAB Cystic Fibrosis Center and the National Cancer Institute (NCI), it is a simple step to send these organizations crude organic extracts and pure compounds extracted from the Antarctic marine organisms we are examining in the course of our ecological studies.

After all, it is not hard to imagine that the evolutionary forces that select for novel chemical compounds that deter a predator or prevent smothering by another organism could similarly yield compounds that break down organic materials, or slow or inhibit cell growth. Such outcomes could prove important when seeking new therapeutic drugs to treat diseases such as cystic fibrosis or cancer.

Among the groups of common bottom-dwelling invertebrates that we have been studying in Antarctica are the ascidians or "tunicates", the latter term derives from the outermost body coat or layer known as a "tunic". The swimming "tadpole" offspring of these sponge-like marine organisms bear a close resemblance to vertebrates, but upon metamorphosis into sedentary adults such similarities vanish in an ontogenetic revolution.

As adults, tunicates are vulnerable to mobile predators such as voracious Antarctic sea stars. They lack a hard protective outer shell that would shield against the action of digestive enzymes released by the extruded stomachs of sea stars. As such, tunicates are prime candidates for chemical defenses, and indeed studies in temperate and tropical seas, as well as our own studies in the Southern Sea, have substantiated this theory.

One of the most common tunicates in the vicinity of Palmer Station is known in scientific nomenclature as Synioicum adareanum. In some locations individuals of this colonial species literally carpet the bottom of the sea, numbering in the hundreds and even thousands of individuals. Recently, our Natural Products Chemist and University of South Florida co-team leader, Dr. Bill Baker, along with one of his graduate students, Thushara Diyabalange, discovered a novel chemical in the body tissues of this abundant Antarctic tunicate.

The molecular structure of this compound placed it among a chemical group known to chemists as polyketide amides. Nameless, the new compound was soon christened "Palmerolide", its etiology rooted in both its discovery near Palmer Station, Antarctica, and its unique chemical structure. As with all novel compounds we describe in the course of our ecological studies, we sent it off for routine screening by the NCI.

You can imagine our surprise when scientists with the NCI contacted us several months later to inform us that Palmerolide was both remarkably potent and had highly targeted activity against melanoma, a deadly form of skin cancer. Its high potency was exciting because it was active against melanoma cells at concentrations well below those that would harm non-cancerous cells (an enticing result considering many cancer drugs are also toxic to healthy cells). Its high specificity for melanoma suggested a mechanism of action that had drug development potential.

The NCI next asked us to send them more Palmerolide so they could re-test the pure compound to ensure what they had observed was indeed a dependable result. Re-testing not only verified the potent nature of Palmerolide against melanoma, but expanded its known activity to 4 of 7 different types of melanoma. Currently the NCI is comparing the broad patterns of bioactivity of this compound with patterns of other known toxic compounds to see if this sheds light on just how Palmerolide is able to both inhibit and kill cancer cells.

The NCI is also conducting “tube tests” placing cancerous cells into small porous tubes which are inserted into mice that have been injected with Palmerolide to see if the compound finds its way into the tube-sequestered cancerous cells. Such “delivery potential” is important to ascertain if Palmerolide were to be considered for development into a cancer drug. If all goes well, future studies would develop techniques to synthesize Palmerolide in the laboratory, thus precluding the need to harvest tunicates, an endeavor both commercially infeasible and of potential environmental concern.

Where the study of this unique Antarctic tunicate compound with anti-cancer activity will lead nobody knows. Nonetheless, for the time being we remain excited about this anti-cancer compound discovered mid-stream in the course of our marine ecological studies. Importantly, if a cancer drug were to be developed, it would be yet another example of how the pursuit of knowledge grounded in the basic sciences plays so critically into discoveries with direct applications to humankind.


TitleFromClick here to change to descending sortDate Posted
Re: A Tunicate Anti-Cancer DiscoveryMarkus and Aikku Ahonen4/7/2004 8:32:48 PM

Dr. McClintock,
We are visiting friends in Birmingham. We live in Helsinki, Finland. We were shown the UAB Antarctica web site and have found it interesting. Your possible anti-cancer find is exciting. If all goes well with tests, do you have any idea how long it might take to become an available drug for use in fighting melanoma? Also we wonder if you have dived for marine life in any other very cold waters besides Antarctica?
Good Luck!

From J McClintock, Posted On 4/7/2004 8:32:50 PM

Dear Helsinkians! Great to hear that are enjoying a visit to Birmingham. I am delighted that you found our interactive Antarctic web site interesting. We share your excitement about our discovery of the anti-cancer compound palmerolide from an antarctic tunicate. The testing road to drug development is long and winding, although the federal goverment has done some things recently to shorter the path. Nonetheless, it is still measured in numbers of years. It is also very costly as it involves funding the synthesis of the compound, testing in mouse and then human trials, and then prouduction and marketing. That said, we remain hopeful that our compound could prove useful as a drug someday. I have been diving in a variety of locations around the world. My home state of California has remarkably cold water due to the Humbolt Current that sweeps down the coast from the north. Moreover, upwelling brings very cold waters to the surface. So I would argue that my central California diving experiences around Monterey, for example, have been in pretty cold waters. Of course nothing gets much colder than the waters of McMurdo Sound, Antarctica, where I have logged a number of dives at temperatures several degrees below freezing (the sea water is not frozen because salt lowers the freezing point a few degrees). Hope you enjoy your stay in Birmingham. My best to you from "the ice"!

Re: A Tunicate Anti-Cancer DiscoveryDee Hellmers4/8/2004 8:52:54 AM

Dr. McClintock, This is the third of your Antarctic expeditions that my students and I have followed via the UAB web site. The journal entries are well-planned, interesting, and very informative. We have been amazed at the photos your team has included so far during this trip. It makes us almost feel like we are there with you! Thank you for enhancing our science curriculum. We are looking forward to reading more about your scientific research, Antarctic wildlife, and what it is like to live and work at a research station. My second graders send you their regards, and they hope you will stay safe. Have a very productive research trip and have fun, too!

From J McClintock, Posted On 4/8/2004 8:52:55 AM

Dee, What a pleasure to hear from you and your second graders as I sit here on this windswept Antarctic morning overlooking the glacier from my office window. Your kind comments across thousands of miles warm the day! I am so pleased that you and your students continue to enjoy our journal entries and photographs. Tell your students to keep their eye out for my next journal entry. It will highlight the work of two whale biologists who traveled here with me aboard ship. They study a variety of aspects of whale biology but especially whale songs! Cheers from "the ice"! Jim

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The researchers completed their expedition in May 2004. Feel free to search this site for their archived journals and responses to questions.

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