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An Overview of Marine Drug Discovery by John Reed, Shirley Pomponi & Amy Wright Division of Biomedical Marine Research Harbor Branch Oceanographic Institution Deep-water marine habitats are a relatively untapped resource for the discovery of novel chemical compounds with pharmaceutical potential. Given that 30% of the drugs now being used are based on natural products discovered in plants and animals on land, and that the oceans remain 
largely unexplored especially compared to land habitats, the potential for finding important new compounds in the marine environment is
tremendous. Over the past quarter century, more than 10,000 compounds, encompassing a massive array of different chemical structure types,
have been discovered in marine organisms. At least twelve of these compounds are currently being tested in human trials for use as
anticancer agents. These include: ecteinascidin from the sea squirt (tunicate) Ecteinascidia turbinata, which is in the final stage of
study before a drug can be made available to the public, known as Phase III trials; aplidine from the sea squirt Aplidium albicans, which
is in Phase II trials; dolastatin from the sea hare Dolabella auratium, which is in Phase I clinical trials; and bryostatin from the bryozoan
Bugula neritina, which is in Phase I/II clinical trials.
Harbor Branch Oceanographic Institution (HBOI) has had an on-going drug discovery research program since 1984. We have collected organisms throughout the world with a focus on deep water (>150 m) tropical Caribbean and Atlantic species. Research on these organisms has led to publications describing over 100 chemical structures and awards to the institution and its researchers of over 90 patents. One of the more notable compounds discovered at HBOI is discodermolide, a potent antitumor agent from the deep-sea sponge Discodermia spp. This compound has been licensed to Novartis and is in Phase I clinical trials for the treatment of cancer. 
Other compounds of interest are the ecteinascidins, potent antitumor agents which are currently in Phase III clinical trials for the treatment
of cancer, and the topsentins, powerful anti-inflammatory agents discovered by HBOI scientists in collaboration with Professor Bob Jacobs of
University of California - Santa Barbara. Topsentins were first isolated from the sponge Spongosorites ruetzler and are under development for
use as additives in anti-inflammatory skin creams. A fourth series of compounds under investigation for the treatment of cancer is the lasonolides.
These compounds, which have shown cancer-fighting potential, come from the sponge Forcepia, which most commonly occurs in Gulf of Mexico
deep-sea habitats.
Reaching the point where the medical potential of chemicals discovered in marine organisms is known is a complex and time-consuming process that often takes us to new and exciting locations. One of the first steps in that process is planning an expedition to search for new organisms. This begins with a thorough review of the scientific literature about a new target site. This can include surveys by environmental consulting firms; information from government agencies such as Minerals Management Service, National Marine Fisheries, U.S. Geological Survey; and research papers from various institutions on the biology and geology of a region. This helps us determine whether an area is worth spending precious time and funds to explore. 
Once an expedition is underway, we collect samples mainly using HARBOR BRANCH's deep-diving submersibles, but also by scuba diving in shallower
areas. The process of studying organisms collected begins as soon as we reach the surface. Each sample is given a unique identifying number and
then quickly frozen. Some pieces of these samples are thawed and studied aboard the ship to determine if they produce chemicals that can kill
microbes during controlled tests. This offers an initial quick indicator of whether or not the chemicals produced by a given organism are bioactive,
a term used to indicate when a compound has an effect, generally a toxic one, on living cells. Other pieces are subjected to more detailed studies
after an expedition in laboratories at HARBOR BRANCH and our collaborators' facilities. This later work involves more sophisticated study of not
only bioactivity, but also the genetic structures of compounds that show promise. A portion of each sample collected is also stored as part of
our extensive archive built up over decades of work, that is housed in a massive freezer in a hurricane-proof bunker. These pieces are archived
so that they can be examined in future studies as new technologies and methods for drug discovery are developed.
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