Joseph H.Hulse Trends in Food Science Technology 15(2004)3-18 9 the USA created for research to explore and exploit improved by computer modelling.Diagnostic processes DNA.Between 1981 and 1999,specialist bioscience are enhanced and speeded up by molecular modelling,by companies in the USA grew from 80 to over 1270.Ernst DNA microchips,and by recent advances in genomics,a and Young report 1180 such enterprises among EU name coined in 1980. member countries.Many evolved from university Drugs synthesized by GM organisms include vac- bioscience departments.Some were highly successful. cines,immune regulators,substances to control cardio- others with insufficient venture capital,and inexper- vascular disorders and various hormones.Modern ienced management,did not survive.Academic scientists vaccines include (1)toxoids-inactivated toxins extracted with ambition to own a specialist bioscience company from cultured pathogens (for tetanus and diphtheria); should have access to deep cash pockets.Risks are high (2)attenuated pathogens (for pertussis-whooping and profitable innovations do not come quickly. cough);(3)isolated biochemically modified antigens of The biomedical industry now consists of two inter- various novel applications.Vaccines from GM viruses related entities:(1)large pharmaceutical corporations(2) include whole virions (poliomyelitis);split vaccines specialist bioresearch enterprises,described as 'Second (influenza);isolated antigens (hepatitis B). generation biotechnology companies'.In 2001,total Recent additions to the biosciences lexicon include revenue of the six largest bioscience companies was ca 'Genomics'-study of genomes and DNA nucleotide $8 billion;research and development investment sequences;Proteomics'-related to specific proteins pro- between 20 and 37%of revenue.They devise and duced by genomes;'Metabolomics'-influence of gene develop new processes and products to pilot plant and expression on metabolites:Transcriptomics'-profiling preclinical stages.Pharmaceutical companies expand of gene expressions using DNA/RNA micro assays. the processes and subject the products to in vitro and in vivo clinical trials to determine potency,reliability and Bioengineering processes safety.For a new drug to progress from the laboratory The immense diversity of active products from bio- to final approval may cost between $300 million and technologies includes whole viable or attenuated cells. $800 million and take between 10 and 15 years. metabolites within cells or diffused into the culture medium. Biotechnologies:future prospects Typical industrial processes progress through several Over the past 20 years,biotechnologies have evolved stages: from intellectually intriguing biosciences into diversifying industries that produce useful biologicals from biocata- i.Identification and isolation of cells to be cul- lytic reactions,genetically modified bacteria,funghi, tured. viruses,plant,mammalian and insect cells.Some tech- ii.Determination of optimum culture and harvesting niques modify genetic composition and expression:oth- systems. ers accelerate and adjust metabolic processes.Of mi. Scale-up to large batch or continuous bio- particular interest to bioengineers are reliable means to reactors. expand from laboratory to factory scale,and technolo- iv. Down-stream processes for fractionation, gies for the isolation,purification and sterilization of extraction,purification and sterilization. end products.Equally critical are reliable systems of V. Methods for process control and product quality. product quality and process control. vi.Protocols to ensure safety and containment Earlier processes of extracting,screening and chemi- throughout development and production. cally modifying natural biochemical substances are giv- ing way to identification of how specific diseases are The over-riding objective is to maximise economic caused,how particular drugs act to prevent or cure yield of stable effective products.A bioengineer with them.More effective diagnostics,prophylactics and many years of experience recently said:"Even where therapeutics are being designed and synthesized by genetic modifications,laboratory and pilot plant trials molecular modelling and combinatorial biochemistry. are entirely successful,scale-up to an economically effi- In the past,an organic chemist might synthesize 50 new cient industrial process is inevitably frustrating,more compounds in a year,computer-assisted modern bio- costly and time-consuming than was forecast." chemistry can generate several thousand.Computers In addition to synthesis by microorganisms,develop- devise molecules to be systematically compared with ments are progressing with cells from higher plants, computer-stored molecular structures.One company animals,insects and GM viruses.Bacteria and viruses screens a million compounds against a target protein are cultured for metabolite synthesis,and for use as every 6 months. vectors to transfer genes between organisms.Cells may Rapid biological screening makes use of membranes be cultured in batch bioreactors or in continuous sys- from human or animal organ cells grown in tissue cul- tems where the nutrient medium percolates through or ture.Immunogenicity of specific antibodies can be over and is transformed by the immobilized cells.Simi-the USA created for research to explore and exploit DNA. Between 1981 and 1999, specialist bioscience companies in the USA grew from 80 to over 1270. Ernst and Young report 1180 such enterprises among EU member countries. Many evolved from university bioscience departments. Some were highly successful, others with insufficient venture capital, and inexper￾ienced management, did not survive. Academic scientists with ambition to own a specialist bioscience company should have access to deep cash pockets. Risks are high and profitable innovations do not come quickly. The biomedical industry now consists of two inter￾related entities: (1) large pharmaceutical corporations (2) specialist bioresearch enterprises, described as ‘Second generation biotechnology companies’. In 2001, total revenue of the six largest bioscience companies was ca $8 billion; research and development investment between 20 and 37% of revenue. They devise and develop new processes and products to pilot plant and preclinical stages. Pharmaceutical companies expand the processes and subject the products to in vitro and in vivo clinical trials to determine potency, reliability and safety. For a new drug to progress from the laboratory to final approval may cost between $300 million and $800 million and take between 10 and 15 years. Biotechnologies: future prospects Over the past 20 years, biotechnologies have evolved from intellectually intriguing biosciences into diversifying industries that produce useful biologicals from biocata￾lytic reactions, genetically modified bacteria, funghi, viruses, plant, mammalian and insect cells. Some tech￾niques modify genetic composition and expression; oth￾ers accelerate and adjust metabolic processes. Of particular interest to bioengineers are reliable means to expand from laboratory to factory scale, and technolo￾gies for the isolation, purification and sterilization of end products. Equally critical are reliable systems of product quality and process control. Earlier processes of extracting, screening and chemi￾cally modifying natural biochemical substances are giv￾ing way to identification of how specific diseases are caused, how particular drugs act to prevent or cure them. More effective diagnostics, prophylactics and therapeutics are being designed and synthesized by molecular modelling and combinatorial biochemistry. In the past, an organic chemist might synthesize 50 new compounds in a year, computer-assisted modern bio￾chemistry can generate several thousand. Computers devise molecules to be systematically compared with computer-stored molecular structures. One company screens a million compounds against a target protein every 6 months. Rapid biological screening makes use of membranes from human or animal organ cells grown in tissue cul￾ture. Immunogenicity of specific antibodies can be improved by computer modelling. Diagnostic processes are enhanced and speeded up by molecular modelling, by DNA microchips, and by recent advances in genomics, a name coined in 1980. Drugs synthesized by GM organisms include vac￾cines, immune regulators, substances to control cardio￾vascular disorders and various hormones. Modern vaccines include (1) toxoids-inactivated toxins extracted from cultured pathogens (for tetanus and diphtheria); (2) attenuated pathogens (for pertussis—whooping cough); (3) isolated biochemically modified antigens of various novel applications. Vaccines from GM viruses include whole virions (poliomyelitis); split vaccines (influenza); isolated antigens (hepatitis B). Recent additions to the biosciences lexicon include ‘Genomics’—study of genomes and DNA nucleotide sequences; ‘Proteomics’—related to specific proteins pro￾duced by genomes; ‘Metabolomics’—influence of gene expression on metabolites; ‘Transcriptomics’—profiling of gene expressions using DNA/RNA micro assays. Bioengineering processes The immense diversity of active products from bio￾technologies includes whole viable or attenuated cells, metabolites within cells or diffused into the culture medium. Typical industrial processes progress through several stages: i. Identification and isolation of cells to be cul￾tured. ii. Determination of optimum culture and harvesting systems. iii. Scale-up to large batch or continuous bio￾reactors. iv. Down-stream processes for fractionation, extraction, purification and sterilization. v. Methods for process control and product quality. vi. Protocols to ensure safety and containment throughout development and production. The over-riding objective is to maximise economic yield of stable effective products. A bioengineer with many years of experience recently said: ‘‘Even where genetic modifications, laboratory and pilot plant trials are entirely successful, scale-up to an economically effi- cient industrial process is inevitably frustrating, more costly and time-consuming than was forecast.’’ In addition to synthesis by microorganisms, develop￾ments are progressing with cells from higher plants, animals, insects and GM viruses. Bacteria and viruses are cultured for metabolite synthesis, and for use as vectors to transfer genes between organisms. Cells may be cultured in batch bioreactors or in continuous sys￾tems where the nutrient medium percolates through or over and is transformed by the immobilized cells. Simi￾Joseph H. Hulse / Trends in Food Science & Technology 15 (2004) 3–18 9