modified nucleosides,spongothymidine to pharmaceutical partners for clinical tional sense.These molecules are now and spongouridine,from the sponge development,manufacture,and sales. being shown by academic researcher Cryptotethia crypta(Bergman and Fee- Of particular importance over the to possess diverse and highly complex ney,1951).These compounds possessed past 15 years is the NCI's"National Co. pharmacological properties with appli activities,and over the operative Drug Discovery Groups"or cations to many diseases.Many unique decades were the inspiration for the de- NCDDGs,and productive researchers molecular probes with activities relevan velopment to two related antiviral drugs such as G.R.Pettit at Arizona State Uni- to fundamental processes have been Ara-A (Vidabarine)and Ara-C. versity's Cancer Research Institute,who isolated and defined.The problem of As might be expected,the large phar- have dedicated their work to cancer-drug developing a greater diversity of marine maceutical industries have had only discovery(Figure 6).The NCDDG col drugs lies in the lack of funding for th modest interest in embracing marine laborative grants were cleverly crafted discovery of drug leads in other thera- drug discovery.This area continues to the close ration of peutic areas.As of 06,the NCI is the day to be one of uncertainty and high academic researchers and industrial only NIH institute that had a dedicated predicted risk,and one that industry has scientists,whose respective abilities to drug-discovery program(Cragg et al, not learned to reliably control.Asa con- focus on new source for possible drugs 2005).Furthermore,there is an unde sequence,more and more discoveries are were coupled with the pharmacological veloped relationship between those who being made by academic researchers and strengths ind develo ntal expe ertise of discover new marine molecules and by the flourishing small biotechnology industry.The result has been productive those who have the biological expertise industries(see Toledo et al.case study. collaborative programs that link these and screening capacity to develop new this issue).Increasingly,the large phar avors(Figure 7). drugs in diverse therapeutic areas.Im maceutical industries rely on the "in- Table 1 lists the cancer drugs discovered pressively,three new marine drugs are in licensing"of drugs discovered in these and related prog ams,their clinical trials for acute pain,three more (Table 1).Thus,in the decades to come,it sources,and discoverers.Seventeen novel are in clinical evaluation for the treat can be predicted that marine biotechnol- molecules,produced by marine bacteria. ment of asthma,and one drug is in clini- ogy companies will evolve as opportuni sponges,as idians,mollusks,bryozoans cal assessment for Alzheimer's Disease ties arise to exploit marine biodiversity. and sharks.are currently in clinical trials. (Table 1).Other molecules are being Cancer continues to be a major disease This impressive list can leav no doubt shown to be effective against malaria and worldwide;in the United States,Europe, that the oceans have the ability to offer other infectious diseases.Indeed,today, and lapan it is a major cause of human new pharmaceuticals,particularly for the the study of bioactive marine molecules mortality.It is thus no surprise that the treatment of cance continues at a spectacular pace(Blunte NCI has invested heavily over the past It is often asked why marine sources al,2003.2004.2005). three decades in the discovery and de- should yield new antica agents?Is it While the ocean is clearly a new fron velopment of anticancer drugs from ma simply that the oceans contain many po- tier in drug discovery,it remains isolated rine sources(Cragg et al,2005).What is tent toxins,and these are useful in killing from the mainstream discovery and de. not widely known is the degree of their cancer cells but have no other utility? velopmental processes,which require success.In 2006,more than 30 marine This is an inaccurate view of the medical hundreds of millions of dollars of in- derived molecules are in preclinical de potential of the orld's oceans created by vestment.How can we change this?One velopment or clinical trials against a wide the significant funding available world can predict that the next decade will see diversity of cancers.A significant number wide to discover new anticancer drugs. major changes in the pharmaceutical of these new drug candidates was devel- Marine life produces a m industry and in how NIH will respond to oped with direct or indirect NCI assis- of complex,bioactive molecules only a medical discoveries and human medical tance,and once brought to the point of small percentage of which is"toxi"to needs.More academia-industry linkages perceived utility,they were then humans and other species in the tradi- will be observed,and the responsibility Occanography I Vol 19.No.2.June 2006 115Oceanography Vol. 19, No. 2, June 2006 115 modifi ed nucleosides, spongothymidine and spongouridine, from the sponge Cryptotethia crypta (Bergman and Fee￾ney, 1951). These compounds possessed unique antiviral activities, and over the decades were the inspiration for the de￾velopment to two related antiviral drugs, Ara-A (Vidabarine) and Ara-C. As might be expected, the large phar￾maceutical industries have had only modest interest in embracing marine￾drug discovery. This area continues to￾day to be one of uncertainty and high predicted risk, and one that industry has not learned to reliably control. As a con￾sequence, more and more discoveries are being made by academic researchers and by the fl ourishing small biotechnology industries (see Toledo et al. case study, this issue). Increasingly, the large phar￾maceutical industries rely on the “in￾licensing” of drugs discovered elsewhere (Table 1). Thus, in the decades to come, it can be predicted that marine biotechnol￾ogy companies will evolve as opportuni￾ties arise to exploit marine biodiversity. Cancer continues to be a major disease worldwide; in the United States, Europe, and Japan it is a major cause of human mortality. It is thus no surprise that the NCI has invested heavily over the past three decades in the discovery and de￾velopment of anticancer drugs from ma￾rine sources (Cragg et al., 2005). What is not widely known is the degree of their success. In 2006, more than 30 marine￾derived molecules are in preclinical de￾velopment or clinical trials against a wide diversity of cancers. A signifi cant number of these new drug candidates was devel￾oped with direct or indirect NCI assis￾tance, and once brought to the point of perceived utility, they were then licensed to pharmaceutical partners for clinical development, manufacture, and sales. Of particular importance over the past 15 years is the NCI’s “National Co￾operative Drug Discovery Groups” or NCDDGs, and productive researchers such as G.R. Pettit at Arizona State Uni￾versity’s Cancer Research Institute, who have dedicated their work to cancer-drug discovery (Figure 6). The NCDDG col￾laborative grants were cleverly crafted to require the close collaboration of academic researchers and industrial scientists, whose respective abilities to focus on new sources for possible drugs were coupled with the pharmacological strengths and developmental expertise of industry. The result has been productive collaborative programs that link these diverse scientifi c endeavors (Figure 7). Table 1 lists the cancer drugs discovered in these and related programs, their sources, and discoverers. Seventeen novel molecules, produced by marine bacteria, sponges, ascidians, mollusks, bryozoans, and sharks, are currently in clinical trials. This impressive list can leave no doubt that the oceans have the ability to offer new pharmaceuticals, particularly for the treatment of cancer. It is often asked why marine sources should yield new anticancer agents? Is it simply that the oceans contain many po￾tent toxins, and these are useful in killing cancer cells but have no other utility? This is an inaccurate view of the medical potential of the world’s oceans created by the signifi cant funding available world￾wide to discover new anticancer drugs. Marine life produces a massive diversity of complex, bioactive molecules only a small percentage of which is “toxic” to humans and other species in the tradi￾tional sense. These molecules are now being shown by academic researchers to possess diverse and highly complex pharmacological properties with appli￾cations to many diseases. Many unique molecular probes with activities relevant to fundamental processes have been isolated and defi ned. The problem of developing a greater diversity of marine drugs lies in the lack of funding for the discovery of drug leads in other thera￾peutic areas. As of 2006, the NCI is the only NIH institute that had a dedicated drug-discovery program (Cragg et al., 2005). Furthermore, there is an unde￾veloped relationship between those who discover new marine molecules and those who have the biological expertise and screening capacity to develop new drugs in diverse therapeutic areas. Im￾pressively, three new marine drugs are in clinical trials for acute pain, three more are in clinical evaluation for the treat￾ment of asthma, and one drug is in clini￾cal assessment for Alzheimer’s Disease (Table 1). Other molecules are being shown to be effective against malaria and other infectious diseases. Indeed, today, the study of bioactive marine molecules continues at a spectacular pace (Blunt et al., 2003, 2004, 2005). While the ocean is clearly a new fron￾tier in drug discovery, it remains isolated from the mainstream discovery and de￾velopmental processes, which require hundreds of millions of dollars of in￾vestment. How can we change this? One can predict that the next decade will see major changes in the pharmaceutical industry and in how NIH will respond to medical discoveries and human medical needs. More academia-industry linkages will be observed, and the responsibility