[From CASE Reports, Vol. 11, No. 3, 1996]

CASE Annual Forum:
Promoting Biotechnology Enterprises in Connecticut

"State's biotech future is bright," proclaims the headline for an article in the Connecticut Post on June 25, 1996. That's good news for the state's economy, which has taken a beating in recent years. Speakers at the Connecticut Academy for Science and Engineering's 1996 Annual Forum, held on June 26 at Bristol Myers-Squibb's Wallingford research facility, described specific ways that the biotechnology industry in Connecticut is helping the economy of Connecticut to grow.

The Impact of Biomedical Technology on Connecticut's Economy

James Keirns, Director of Drug Metabolism and Pharmacokinetics at Boehringer Ingelheim Corporation and Vice Chairman of the Connecticut United for Research Excellence (CURE), presented the results of two recent studies undertaken by CURE. The first CURE Report, issued in March of 1996, emphasized the importance of biomedical research in Connecticut. According to this report, one of Connecticut's strengths for the future lies in the biomedical research sector, which comprises the pharmaceutical companies, biotechnology firms, and academic research institutions and medical centers.

"The CURE report shows that four Connecticut pharmaceutical companies have a combined annual Connecticut-based research and development investment of more than $1.2 billion-that's more than 10% of the total domestic research and development budget for pharmaceuticals in the United States," said Dr. Keirns. In addition, Connecticut's research universities receive large amounts of government and private research funding: Connecticut ranks fourth behind Massachusetts, Maryland, and Washington, in awards per capita from the National Institutes of Health.

Despite its leadership position in pharmaceutical research and development and academic research, said Dr. Keirns, Connecticut falls far below the national average for biotechnology growth. According to the CURE report, Connecticut spends only 20% of its academic research funds on biotechnology research, while Massachusetts spends 283% and California spends 321%; the national average is 72%. "Connecticut has research strengths, located mainly at the University of Connecticut and Yale, that it's not capitalizing on," said Dr. Keirns. "Helping to transfer some of these academic assets to the private sector is an important next step in stimulating the economy of the state."

The CURE report offers some recommendations for stimulating private sector investment in basic research and infrastructure to help develop biomedical research in Connecticut. CURE suggests that the state play the role of facilitator, by supporting, encouraging-and adding the weight of its legislative and executive powers- to the needs of the private sector. These recommendations include: 1) streamlining the procedures for state and local regulatory requirements and grant applications by identifying a single contact office for applications; 2) establishing economic policies to attract, retain, and grow the biomedical research enterprise, and; 3) promoting the sector by supporting basic academic research and eliminating federal regulatory inefficiencies.

At a conference on June 24, CURE presented a set of specific strategies aimed at strengthening and growing the biotechnology segment of the Connecticut economy. "One big problem for small companies is finding space," noted Dr. Keirns. "The first of the recommendations from this conference is to help with facilities expansion through a loan/lease program that will increase the quality and amount of suitable space for biotech company development." The second recommendation is to help with technology transfer from universities to the private sector through a matching program that will increase the volume of company-sponsored projects at the universities. The third recommendation is to improve the operating environment for small companies through tax relief that will encourage companies to locate in Connecticut.

"Implementation of these recommendations should provide an economic environment in Connecticut that would encourage the growth of biotechnology companies here," said Dr. Keirns, "and it could have great results in terms of jobs and tax relief." The projections reported by CURE include: 1) net dollar benefits to the state of $19.5 million; 2) nearly 1000 direct biotechnology jobs; 3) approximately 2600 indirect biotechnology jobs, and; 4) approximately 75 academic jobs. "This is a continuing process," Dr. Keirns said, "and CURE is looking forward to working with CASE to help move this along."

According to the March CURE report, human therapeutics and human diagnostics are the largest areas in biotechnology research, although agriculture and other specialty areas are rapidly growing and may play an important role in stimulating Connecticut's economy, as was clearly demonstrated by the other speakers at the CASE Forum.

Agricultural Biotechnology-Improving Crop Value Through Biotechnology

Christopher Flick, Director of Research for DEKALB Genetics Corporation, discussed the potential uses for biotechnology in crop production, using DEKALB as a model. Dr. Flick described DEKALB, the second largest corn feed company in the United States, as being "in the genetics business." In the past, companies like DEKALB have used plant breeding to provide variety in their crops; more recently, they have begun to use genetic engineering techniques to develop hybrid plants with characterisics that were not previously possible, such as herbicide and insect resistance and enhanced nutritional value.

The techniques used by DEKALB are relatively simple, standard cell culture and molecular biology procedures during which scientists remove cells from corn plants, introduce genes for the desired trait, and grow the cells up in culture. The cells produce new plants from which the researchers obtain seeds that have the desired trait

At DEKALB, researchers have developed a strain of corn that is resistant to herbicides-a characteristic which, because it was perceived as one of the easiest to alter, was tackled first. The first recombinant herbicide-resistant corn plant, sold by DEKALB, went to market in 1996. Other herbicide-resistant crops, like soybeans, are expected to reach the market over the next few years.

DEKALB is also marketing new insect-resistant corn hybrids to farmers this year; these produce a 10–20% higher yield than conventional plants. The main insect pest for corn plants is the European corn borer (ECB), which eats the leaves and stalk of the corn plant, killing it. The hybrid ECB-resistant plant contains the gene for a substance that is toxic to the ECB, and the insects die when they eat the plant. This substance is not toxic to higher animals and presents no danger to wildlife, livestock, or humans. "This provides more effective insect control and is safer for the environment," says Dr. Flick.

Producing plants that require less fertilizer and are drought-resistant are longer-term projects, but, according to Dr. Flick, these seeds will be on the market by the year 2000.

A farmer raising livestock must supplement the corn grain used for feed with amino acids, soybeans, and oil, among other things, to provide a nutitionally complete feed. Researchers at DEKALB have developed corn plants whose seeds have higher levels of the amino acid tryptophan, than seeds from conventional plants.

Regulatory and intellectual property issues are new arenas to plant scientists, noted Dr. Flick, adding, "A lot of time and energy has gone into production of these hybrids and they need patent protection." Companies like DEKALB must also deal with foreign regulatory agencies if they plan to sell their grain overseas.

Aquacultural Biotechnology

Aquaculture is a new technology in Connecticut, according to Professor Thomas Chen, Director of the Biotechnology Center at the University of Connecticut, and has many applications. Aquaculture techniques can be used in food production, and transgenic fish produced using genetic engineering techniques can be used as bioreactors or as models for medical research.

Dr. Chen quoted some statistics in support of using aquaculture for food production. According to the Food and Agriculture Organization, there will be a 40 billion ton shortage of seafood worldwide by the year 2010. In addition, the US trade deficit for edible and nonedible fish products is second only to that for petroleum. "The solution to these problems may be a combination of aquaculture and biotechnology," claimed Dr. Chen. "Aquaculture has been used for 4000 years in China, and we can combine it with recombinant DNA technology to improve the efficiency."

"One potential application would be to farm exotic food fish species that have a high economic value," Dr. Chen said. A typical telapia farm requires 2.5 acres of land and produces 3 million pounds of fish worth 5.5 million dollars. The farm generates 80 jobs and 45 indirect jobs. Other possible applications include farming macroalgae, including nori, wakami, alginates, and carrageenan, for food, or growing ornamental fish.

According to Dr. Chen, successful aquaculture depends on several factors. The farmer must have complete control of the fish's reproductive cycle and must have broodstock with an excellent genetic background. The farmer must be able to efficiently detect and prevent disease, which can represent up to 60% of the expense of a fish farm. The farmer must also have a thorough understanding of the the optimal physiological and environmental conditions for growth and development of the fish. Of course, the farm must have an efficient supply of good quality water. "And, like any business, the fish farm must be run with innovative management techniques," said Dr. Chen.

The important areas for biotechnology in fish farming are in controlling the reproductive cycle and providing broodstock with a good genetic background. The reproductive cycle can be controlled by treating the fish with sex hormones-in this way, the farmer can bring the fish to sexual maturation and collect eggs. Genetic engineering techniques can also be used to increase the size, and therefore the market value, of the fish. Dr. Chen's research has shown that this is possible by injecting fish with growth hormones, and they have also produced transgenic fish, that is, fish that have a growth hormone gene inserted into their genome, so that all of their progeny will have that gene.

Aquaculture could become an important industry for Connecticut, according to Dr. Chen. State officials will have a chance to see when one company, Aquaclear, moves here from Pennsylvania in the near future. "The possibilities are endless," Dr. Chen said. His claim may ring true not just for aquaculture, but for the future of all areas of biotechnology.--Lisa Christenson, science writer.

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