Tokyo Funds Marine Biotechnology Plan

An initiative by Japanese firms and government agencies outpaces U.S. efforts, despite America's head start in the field WASHINGTON -- Try to imagine Motorola, Corning Glass Works, Bethlehem Steel, Merck, and Revlon sitting down at the table with Citibank, Chase Manhattan, Bank of Boston, and a few insurance companies and agreeing to invest more than $90 million in a new research project. Then throw in the federal government, with a matching contribution of $90 million. Such a scenario, implausible for the United States, is just what Japan is doing to boost the nascent but burgeoning field of marine biotechnology. With an eye toward what it calls "the greatest remaining technological and industrial frontier," the Ministry of International Trade and Industry (MITI) has teamed up with 24 Japanese companies and banks on a par with the U.S. companies mentioned above, as well as scientists, to launch the Marine Biotechnology Institute to make a 10-year commitment to the field. The institute is modeled after U.S. programs, the research will build on U.S. discoveries, and the scientists are trained in U.S. laboratories. U.S. pioneers like microbial ecologist Rita Colwell of the University of Maryland and molecular geneticist Daniel E. Morse of the University of California, Santa Barbara, point proudly to multimillion-dollar marine biotechnology centers that they built with the help of far-sighted state officials as the wave of the future. But the U.S. government and corporations are not doing their part in tapping the rich promise of marine biotechnology. The Japanese project is some 10 times larger than that which exists in the U.S. In the U.S., federal and corporate support of marine biotechnology - the application or use of marine organisms or their constituents for useful purposes - is negligible compared with that for more established aspects of biotechnology. And biotechnology budgets as a whole are a pittance compared with budgets in major segments of the nation's R&D budget, such as defense. U.S. scientists, too, may be missing the boat. On the one hand, they contend that the U.S. leads the field and that Japan lacks the creativity of U.S. researchers. But while creativity can produce discoveries that eventually may improve the nation's economic competitiveness, advances often depend less on inspiration and more on dogged elaboration of new insights and refinement of new ideas. Unhappily for the U.S., support for such advances falls beyond the scope of agencies that give grants for basic studies, and of industry interested in developing new products. As a result, some experts fear that Japan's national strategy will prove to be a better approach to harness marine biotechnology than are the piecemeal efforts now underway in the U.S. Just as with semiconductor and electronic technologies, it may be the Japanese who best exploit what marine biotechnology has to offer and who capture billions of dollars in new seafood, specialty chemical, pharmaceutical, enzyme, and waste detoxification markets. "Now that they have understood the potential, they are targeting for a maximal hit [in the marketplace]," says Colwell. "The Department of Commerce should say that this is an area of tech- nology that we should really support to improve our import/export balance. If Congress really understood the amount of money being lost in this country, they would do something about it." Already, for example, Japan has leapfrogged over U.S. investigators who discovered the un- usual organisms residing in deep-sea hydrothermal vents and have isolated the first antibiotic from one of these organisms. Also, Japan has begun a project devoted to exploiting the ability of these "superbugs" to survive under high pressure and high temperatures and is building an institute devoted to the study of this ecosystem. "It's depressing to see the Japanese move ahead," says Dennis Powers, director of Stanford University's Hopkins Marine Station in California. Marine biotechnology is a small, poorly defined subset of biotechnology, so much so that some U.S. policymakers are not even sure what it is, never mind what its potential might be. "We don't use the term at all, we call it marine microbiology," Robert W. Newburgh, director of biological sciences at the Office of Naval Research. "Biotechnology is a buzzword." In the U.S., this subset encompasses a few people spread across many disciplines. Lacking a coherent voice, their cries for support are barely heard by industry and federal agencies. The novelty that makes marine organisms such rich sources of new products also makes harnessing these products a greater challenge. Recognizing this potential, Japan is luring chemists, engineers, microbiologists, pharmacologists - investigators with no background in marine sciences - to the sea. During the past three years, Japanese scientists have toured the top marine laboratories in the United States to plan their own efforts, pulled together an international society, and even hosted the first marine biotechnology meeting, which last fall attracted 300 participants from all over the world Scientists also plan to start a journal. "It represents the merging of many different sectors," says Oskar Zaborsky of the National Research Council. "These efforts are breaking new ground in trying to develop this marine biotechnology." MITI and 24 Japanese companies have set up the Marine Biotechnology Institute to oversee the work. The institute, in turn, has created a two-laboratory Research Center for the Industrial Utilization of Marine Organisms. Due to open their doors next month, the labs cost $21 million each, and each will have a staff of 50, some of whom are scientists from member companies. One lab is located on the country's eastern coast at Kamaishi, where the water is cold. The other lab is at Shimizu, where there are warm currents. The first will survey marine organisms for biological active substances and develop culturing and breeding technology. At Shimizu, scientists will work to understand the chemistry of substances found in the sea. The institute is just one of several thrusts in marine biotechnology in Japan. The 20-year-old Marine Science and Technology Center is building a $12 million lab complete with a hyperbaric research facility and a submersible vessel and will devote a major part of its $80 million annual budget to explore hydrothermal vents and to collect, culture, and understand deep sea organisms. Japan's Ministry of Agriculture, Forestry and Fisheries, the counterpart of the USDA, will operate a third marine biotechnology institute with 30 scientists and a $20 million-a-year budget to develop better ways to use marine organisms and, in particular, to use waste parts from edible species. Japan is betting heavily that this science will yield new commercialopportunities, more so than protein engineering, which is considered to be a main source of biotechnology's next generation of products. MITI invests less than $5 million a year in its Protein Engineering Research Institute, which is another joint effort with industry and academia, compared to the $17 million a year for marine biotechnology. The idea is that, eventually, new commercial opportunities based on science will come out of these projects, opportunities that individual companies will exploit. Plant physiologist Akira Mitsui, who with Zaborsky toured these facilities, credits MITI for lining up Japanese companies and other government agencies behind this marine biotechnology objective. The carrot: If companies could work together, then the Japanese government would foot half the bill for the institute and a research ship. About a half-dozen large companies signed up at first, but more are getting involved each year. The institute will do the research and hold the rights to inventions made there but will license these advances to companies for development. The joint effort in Japan has long-term objectives, which are essential for this nascent field. "We don't know whether it will work," says Mitsui, who directs the University of Miami International Research Center for Marine Bioscience and Technology. "But it seems to be working very well. They are cooperating." He laughs at the thought of U.S. companies following a similar model. "They [U.S. companies] want the support of the government, but I am not sure they are interested in working together," he says. Other scientists say that U.S. executives have the wrong attitude. "I've talked to a lot of companies," says Dennis Powers, who heads Stanford University's Hopkins Marine Station. "They have this attitude that they want everything for almost nothing and they want exclusive rights." They also want it yesterday. "Big [U.S.] industries are just interested in next year's profits," adds microbial ecologist Rita Colwell, who founded Maryland's Center of Marine Biotechnology. "Japan goes into it for the long haul." --E.P. Whereas the U.S. government spends almost $3 billion a year on biotechnology overall, marine matters get between $6 million and $20 million, depending on one's definition. Although a narrow definition covers only its role in developing useful products, more broadly it refers to the use of molecular biology to answer basic questions in the ocean sciences. That would include molecular probes to understand regulatory mechanisms for reproduction and dispersal of organisms, studies of mitochondrial DNA to map the distributions of organisms, or techniques to trace the fate of greenhouse gases in marine systems. But scientists who pursue funding for such basic questions sometimes forget to make the connection between acquiring knowledge now and manufacturing products later. "Basic research is supported well in the United State; it's where they [the Japanese] get their ideas," says Oskar Zaborsky of the National Research Council. But basic research alone does not lead to reduced trade deficits or economic competitiveness. For the most part, marine biotechnology lies in the no man's land between discovery and product, between "basic" research and product development. For example, fish biologist Thomas Chen of the Center of Marine Biotechnology in Baltimore and Stanford's Powers have isolated and cloned growth hormone genes for fish. "Now I need to make it better, but that's not considered pure research," says Chen, associate director of the center. Since he is beyond making basic discoveries, he can no longer expect the National Science Foundation or the National Institutes of Health to support his research. But he needs three to five more years before he can approach companies and, in good faith, promise the sort of return on their investments that they demand. "That kind of money cannot be had," he complains. "The only way would be for me to form my own company." That problem does not exist in Japan. Officials there focus on a different point of the continuum from basic discovery to marketable product from what they see happening in U.S. labs. In Japan, scientists isolate new microbes and develop ways to culture and store them. They survey the biological activity of substances produced by marine organisms, with particular attention to interesting polymers and potential anticancer and antiviral agents. "I wouldn't call it basic research," says Zaborsky. Nor does he see these endeavors as product development, which rightly fall under the purview of companies. Instead, he and the congressional Office of Technology Assessment call this work "generic applied research," which "goes beyond the means of one company, even one industry, to support," he says. "We're not doing enough generic applied research." Scientists are quick to blame industry for not taking on this task. Federal agencies hide behind their mission to back "basic" research in denying support to projects that are less innovative. "We support [marine biotechnology] by developing the technology base to allow biotechnology to move forward," says Eric Eisenstadt, scientific officer at ONR. "We don't do any applied research." That attitude also reigns at NSF, leaving those scientists like Chen and Powers few places to turn. Consequently, when in 1982 UC-Santa Barbara's Morse discovered a growth hormone that accelerated development in abalone, he couldn't get support to continue the work. Instead, Japanese chemists purified the compound and are now testing it in the field. "That major effort was simply unsupportable in the United States," says Morse. Buzzword or not, marine biotechnology is a frontier with exciting possibilities and daunting challenges. The sea's creatures have evolved different survival techniques than have terrestrial plants and animals. Molecular techniques offer new tools for understanding those solutions and for adapting them to our own needs. Marine organisms ward off disease and infections with substances much different from current drugs. Their metabolisms harness enzymes that function more efficiently and under more adverse conditions - such as toxic environments - than do those used by landed creatures. They have different means for converting sunlight to chemical energy and a variety of unusual cellular products. But taming this frontier will not be easy. "The important thing is to do it step by step," says Akira Mitsui, who directs the University of Miami International Research Center for Marine Bioscience and Technology. "A large amount of funds and a long-term effort are necessary. That is what Japan is trying to do." [Editor's note: This is the first of a two-part series on the different approaches taken by Japan and the U.S. to realize the intellectual and commercial potential of marine biotechnology. In the next issue: How the U.S. approach depends on individuals to move the science forward.]

Tokyo Funds Marine Biotechnology Plan

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