U.S. Sluggish In Commitment To Marine Biotechnology

While Japan is bearish on the potentially lucrative field, American government and industry fail to show enthusiasm or backing WASHINGTON -- To promoters of U.S. competitiveness, Japan's Ministry of International Trade and Industry sometimes seems invincible. MITI has an enviable reputation for helping industry develop new products - often based on United States discoveries - that eventually dominate global markets. So MITI's decision to spend almost $200 million in the next decade on marine biotechnology (The Scientist, March 19, 1990, page 1) has raised eyebrows at the U.S. laboratories where this science was conceived. But some U.S. researchers are confident that they can hold their own against this Asian Goliath. They are "the American answer to MITI," says Ronald Cape, board chairman of Cetus Corp., of Emeryville, Calif. But they say they need the backing of the U.S. government and industry. Rita Colwell is one such scientist. In 1985 the University of Maryland biologist approached the Defense Department's Office of Naval Research with a proposal to start a center that would focus on a new hybrid science called marine biotechnology. Until that time, neither the nation's major oceanographic institutions nor the U.S. centers for molecular biology had thought much about the concept. But to Colwell, who had devoted her adult life to understanding marine micro- rganisms, the idea was an imperative. The oceans cover 70 percent of this earth, she argued, and contain a wide variety of organisms with unknown potential as products useful to humanity. The Office of Naval Research agreed with her plan, giving the University of Maryland $6.7 million from its newly created University Research Initiative facilities program to equip the Center of Marine Biotechnology (COMB) in Baltimore. At the same time, Colwell drummed up support from her state and local governments, not just for marine biotechnology, but for biotechnology in general. Today, COMB's 70-member staff strive to make that new science a reality. With a $2.5 million annual operating budget they have developed transgenic fish and biotechnology for improved production of oysters, and have discovered a new polysaccharide glue made from a marine bacterium. And they're thinking big. In the works is the $50 million Christopher Columbus Center, with COMB as its centerpiece. It will stand in Baltimore's Inner Harbor, alongside the acclaimed aquarium and down the block from molecular biologists at Johns Hopkins University. Colwell says her goal is to make her center "a national institute." Colwell is already a national treasure, says Michael Neushul, a California scientist also active in harnessing the sea's products. He believes that she's more than a match for any Japanese agency. As proof, he recounts how the Japanese organized a society for marine biotech-nologists and last year in Tokyo held the first international conference on the topic. But they were upstaged, he says, when Colwell showed up with the premiere issue of the field's first journal, Marine Biotechnology Abstracts. Nevertheless, with U.S. science facing ever tougher competition for research support, it is no surprise that COMB executive director Fred Singleton is worried about his Japanese counterparts. Singleton has hosted more than a dozen delegations from Japan, scientists who want to study COMB before setting up their own centers. "To a large degree, our program here has served as a model," says Singleton. "But they are investing probably 100 times as much as we're investing. "The way the Japanese are doing it, everyone is pitching in," he adds. "When you combine resources, you have a higher probability of success." But U.S. science isn't used to operating in that fashion. "It is a very difficult matter for different companies with different interests to work together," says Akira Mitsui, a marine biologist at the University of Miami who has visited several Japanese laboratories. "Usually the government asks for a proposal from an individual company or an individual investigator." When it comes to funding, marine science takes a back seat to terrestrial studies. And marine biotechnology gets no seat at all. The National Sea Grant College Program, the Office of Naval Research, the National Science Foundation, and the National Cancer Institute all provide small amounts of federal funds for investigations of marine organisms. The work is targeted either toward the development of commercial applications or toward development of a knowledge base that would eventually support marketable products. And it's the latter focus, what might be better called marine molecular biology, for which most scientists would like to see more support. Even though many discoveries never get out of the academic laboratory, they argue, the strength of the U.S. research enterprise lies in basic research. "There is not enough basic science," argues Phillip Taylor, director of the biological oceanography program at NSF. "That [basic research] will help us take more efficient approaches to applications." But the question of who will take those approaches is still an open one. According to Sea Grant's David Attaway, researchers have uncovered many promising unusual marine substances over the past two decades. But their biological or pharmacological features have not yet been evaluated adequately. "It suggests that the United States will make only a weak effort to be an international competitor in marine biotechnology," he wrote in his 1988 report on marine biotechnology. There is little evidence that the situation has improved much in the past two years. Industry has been very slow to recognize - and pay for - the potential of discoveries in the field. And the federal government has not been very generous. NOAA's Sea Grant program is the one federal activity that seeks to stimulate the application of basic research. Scientists like the University of Maryland's Rita Colwell would like to see it expanded as a way of keeping up with what Japan is doing in marine biotechnology. Although it is the federal program most clearly identifiable as doing marine biotechnology, last year it spent just $2.3 million on the field, with an additional $1.7 million in matching funds. That money was spread fairly thin among 58 projects spanning biochemistry and pharmacology, genetic engineering, biochemical engineering, microbiology, and phycology. An even bigger problem for the Sea Grant program was the repeated attempts by the Reagan administration to eliminate it. "We have over the past few years proposed to expand [our efforts in] biotechnology, but since we weren't in the budget, none of our initiatives went anywhere," says Attaway. This year's presidential budget, for the first time in a decade, contains funds for Sea Grant. But the request is at a level - $27.5 million - that's well below its current appropriation of $39 million. And that amount has been held constant since 1981. Sea Grant also spends its money on institutional grants to the 29 Sea Grant colleges and universities, which then distribute them according to their state's priorities. As with the U.S. Department of Agriculture land-grant system, this approach can serve to reinforce the status quo and protect projects that are not always at the cutting edge of science. Because Sea Grant does not earmark support for marine biotechnology, the field tends to get overlooked when the funds are distributed. The National Cancer Institute (NCI), as part of its quest for anticancer (and, more recently, anti-AIDS) agents, is in the middle of a five-year program to collect plants and animals and extract their natural products. NCI spends about $2 million a year to screen these substances for therapeutic potential, and about 3 percent receive additional scrutiny. It has recently awarded the Australian Institute of Marine Sciences a two-year, $1 million contract to collect 1,000 marine organisms for this purpose. NIH gives about $2 million more to individual scientists investigating marine products. The Office of Naval Research's Biological Sciences Division spends about 20 percent of its core program dollars in what can be loosely termed marine molecular biology. For the most part, this $1.7 million supports the use of molecular techniques for basic research. Studies of thermophilic organisms and marine plants and animals that survive in extreme conditions will get an additional $300,000 in 1990 as part of the final year of an Accelerated Research Initiative (ARI). Also, for the past five years, ONR has supported the Center of Marine Biotechnology in Maryland as a University Research Initiative. In 1991, it hopes to start a $1-million-a-year, five-year research effort in marine symbiosis, some of which may involve the use of molecular techniques. But ONR scientific officer Eric Eisenstadt is quick to note that "we don't do any applied research." The National Science Foundation spends about $1 million of its $17 million annual biological oceanography budget on marine biotechnology. Other NSF divisions support marine biotechnology indirectly. For example, the cellular bioscience program spends about $5 million a year on basic studies involving marine organisms. The number of scientists eager to do marine biotechnology, although small, is increasing rapidly, owing in part to new fellowship programs. Last year, for the first time, NSF offered a postdoctoral training program in marine biotechnology and awarded 10 fellowships. So far, California has given the Santa Barbara center $600,000 for two 2-year training grants that have produced about 20 marine biotechnologists. ONR spends about $100,000 on short courses at key marine labs where scientists can learn how to apply molecular techniques to solve ocean science questions. "In total, we're not spending very much money," says William Fenical, a professor of oceanography at Scripps Institution of Oceanography in La Jolla, Calif. "Our efforts are peanuts compared to that of the Japanese." Adds Dennis Powers, director of Stanford's Hopkins Marine Station in California, "We need a national strategy. There should be major initiatives." An NSF committee has recommended that the agency increase spending on research and training in the application of molecular biology to ocean sciences. Two other national reports are in the works. But scientists warn that action, not words, is what's needed most. "The [recommendations] must be implemented soon," says Powers. "If we wait five years, it will be too late." --E.P. That approach works well in most cases, Neushul believes. "Its strength is that it is not a single, monolithic system," he says. Instead, several federal agencies fund marine biotechnology in the course of supporting broader programs (see accompanying story). Colwell, for example, has tapped state and local government coffers to get her center going. Thomas Chen, a scientist at COMB, studies growth in fish with a grant from the National Science Foundation; one outcome is identifying the gene for growth hormone. For his part, Neushul has taken advantage of the federal government's Small Business Innovation Research program to get Naushul Mariculture Inc., a three-person R&D firm focused on marine resources, off the ground, and his home institution, the University of California, Santa Barbara, has just built a new center for marine biotechnology. Even without direction from the federal government, the field is sprouting all over the country. In 1987, UCSB molecular biologist Daniel Morse set up a Marine Biotechnology Center. It has since moved into an $8 million laboratory complete with temperature-controlled running salt-water tanks in clean rooms filled with sophisticated instrumentation. Its 17 faculty and 24 research associates bring in more than $2 million in grants from the National Sea Grant College Program, the National Institutes of Health, NSF, and ONR. The center also receives about $1.5 million each year from the university. At the University of Miami, Mitsui has expanded his research in how microorganisms use solar energy into an international center that searches for new food additives and medicines and marine products for cleaning up pollution or as a source of clean energy. Beginning in 1972, he slowly built up a 17-person project and adopted the long-term goal of harnessing hydrogen as a clean fuel. Most of his support comes from the Department of Energy. More recently, other marine laboratories are recognizing the power of molecular biology. Last year, the Woods Hole Oceanographic Institution (WHOI) and the Marine Biological Laboratory across the street set up the Protein and Nucleic Acid Chemistry Center, a fee-for-services molecular biology laboratory. At the same time, both institutions have been beefing up their staffs with scientists who use molecular techniques in their research. Despite these efforts, Japan may still wind up in control of marine biotechnology. There are "pockets" of marine biotechnology in the U.S., says Phillip Taylor, director of biological oceanography at NSF, "but they are just getting going." In addition, scientists fear that institutions now entering the field may dilute the efforts of those already hard at work. "It's going to be a great shopping center," says Neushul about COMB and the raiding of faculty that will likely go on as the big oceanographic institutions try to catch up. Their resources - and their command of the federal research dollars - could make them more attractive places to work than the sites that pioneered the U.S. effort in marine biotechnology. So far, a relative handful of companies - usually small startups that are themselves underfunded - are involved in tapping marine products. Major companies "are intrigued by what they hear and what they read, but they do not have enough information to formulate good plans," says Oskar Zaborsky of the National Research Council. "Right now, if industry wants to get interested in this, they are going to have to do a lot of legwork. But industry seems to be impatient." W.R. Grace, a $6 billion chemicals corporation, supports research at Maryland's Center of Marine Biotechnology, for example. But that involvement is unusual for a company of such size. "I think there's a huge potential," says Jacob Eyal, a research engineer at Grace's research center in Columbia, Md., "but they [companies] will not go into a field they do not know." Neither will scientists, even though progress in the field, like here in biotechnology, will require greater melding of engineering, chemical, and biological talent. Right now, for example, there's little emphasis on biochemical engineering for organisms from marine environments or on marine organisms for biosensors or biogenerators. Yet such mixing of expertise is crucial to the future of marine biotechnology. Even if a molecular biologist shows interest in an ocean science, there's little funding for cross-disciplinary research. "There's a tendency to be very conservative and to fund projects along traditional lines," says Colwell. "And that's a real problem." One solution is for marine biotechnology to emerge as its own discipline. "We need to focus some attention on it [marine biotechnology] as a field itself and elicit interest in the academic community and in industry and government circles," says David Attaway, acting director of Living Resources at the National Sea Grant College program in NOAA. "We've got to get more things than little proj-ects going if we want to compete with Japan and other countries." For the science to really come into its own, researchers must first take stock of existing expertise, Zaborsky advises. Then they need to organize those experts into an active marine biotechnology community that can lobby for strong, stable funding through either NOAA or NSF's biological oceanography programs. Some scientists think that Sea Grant should dole out the bulk of federal support for this research, says Neushul, but nothing will happen until there's a visible constituency for the money. A step in that direction is a second international meeting, planned for 1991 in Washington, D.C. Last year's initial meeting in Japan spawned a perception that "we're starting to lose some ground relative to Japan," says Dennis Powers, who heads Stanford's Hopkins Marine Station. "So some representatives pushed to have the U.S. be the next center for the conference." But like U.S. marine biotechnology itself, plans for the meeting seem stalled. "We are a little bit behind in getting moving," Attaway admits. "I don't see anyone taking the ball and running with it."

U.S. Sluggish In Commitment To Marine Biotechnology

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