Biotechnology

Biotechnology was defined by the 1981 Federal Task Force on Biotechnology (Brossard Committee) as the "utilization of biological processes, be they microbial, plant, animal cells or their constituents, for the provision of goods and services." In some respects, biotechnological techniques represent adaptations of familiar industrial processes (eg, fermentation). While such processes were used initially to produce potable alcohol, organic acids, solvents and other products (eg, antibiotics, amino acids, vitamins, gums, steroids), recent spectacular advances in MOLECULAR BIOLOGY and GENETIC ENGINEERING have extended their range of application, particularly into health care and food processing.

The Canadian focus on biotechnology began formally in 1983 with the creation of a National Biotechnology Strategy focusing on research relevant to the Canadian economy. This raised the level of cooperation between different areas of research within the sector and encouraged increased investment aimed at exploiting biotechnology's commercial applications. Biotechnology in Canada is now recognized internationally for its innovation and output.

Throughout the world, programs have been vigorously pursued in both the public and private sectors to develop means of using biotechnology in fuel production; recovery of raw materials; crop fertilization and plant breeding; waste treatment and POLLUTION control; development of more effective health-care products, new feedstuffs and new sources of industrial chemicals; and pest control. A number of countries (eg, EC countries, Japan, Israel) have mounted special long-term, government-financed programs in biotechnology, and the US has a commanding lead in the basic biomedical sciences. Individual Canadian scientists have made major contributions, particularly in the field of GENETIC ENGINEERING tools leading to the establishment of the genetic basis of several elusive diseases. In 1993, Dr Michael SMITH was awarded the NOBEL PRIZE for his discovery of site-directed mutagenesis, which allows the artificial manipulation of genes. There is increasing industrial participation in the commercial opportunities offered by these processes.

Techniques

Biotechnology is strongly interdisciplinary, its current strength based on key techniques spawned by interdisciplinary advances in BIOCHEMISTRY, CHEMISTRY, ENGINEERING, GENETICS, MATHEMATICS, microbiology and PHYSICS. These techniques include genetic engineering, industrial enzymes, cell fusion, plant cell culture, and biological process and systems engineering.

Applications

Five major biotechnology process applications are of particular interest to Canada's resource industries: biological nitrogen fixation, cellulose utilization, waste treatment and use, mineral leaching, and development of new plant and animal strains.

Biological Nitrogen

Fixation is increasingly important because of the escalating cost of nitrogen fertilizers. Plant breeding and genetic engineering techniques are expected to produce plants (eg, cereals) capable of symbiosis with nitrogen-fixing bacteria. LEGUMES are the only major family of food plants that naturally possess this ability.

Cellulose Utilization

Canada's large agricultural and forestry resource base offers important and novel opportunities for the use of cellulose (ie, for BIOMASS ENERGY). Cellulose pretreatment processes, coupled with microbiological or enzyme hydrolysis, are receiving industrial attention throughout the world. Cellulose is attractive to Canada because of the size of the forestry industry, which makes a net annual contribution of more than $12 billion to Canada's balance of trade; however, Canada's extensive fossil fuel reserves and consequent relatively low energy prices are expected to provide serious competition to commercial development of cellulose as an energy feedstock for some time.

Waste Treatment and Use

Detoxification of effluent and the transformation of waste to useful products is increasingly important in the evolution of an industrial society. Biological processes offer particular advantages in adapting to varying waste compositions and conditions of degradation.

Mineral Leaching

Microbiological action on mineral sulphides and conversion to more soluble forms have been known for centuries; these methods have already been adapted to the recovery of copper and uranium and will eventually be used for such metals as nickel and zinc (see METALLURGY). The one obvious advantage of biotechnological techniques is their very low energy requirements.

Plant and Animal Breeding

Genetic engineering and cell fusion techniques will prove essential for the future economic development of Canada by providing new plant strains capable of fixing atmospheric nitrogen and exhibiting a greater pest resistance with an earlier maturation, a higher nutritional value, and a greater tolerance to a variety of climatic conditions. Also important is the genetic development of farm stock with improved disease resistance and increased fertility and productivity.

Other Uses

Some chemicals, at present derived from petroleum or coal, will be supplied by biological processes, including cellulosics, microbial polysaccharides, lignin derivatives, lactic and other organic acids, ethanol, acetone, butanol, vegetable oils for plasticizers, lubricants and RUBBER. In addition, certain FOOD ADDITIVES, proteins, fragrances and monomers for specialty PLASTICS and related substances may best be produced by biotechnological techniques. In the areas of fertilizers, herbicides, pesticides, inoculants and vaccines, biotechnology has demonstrated its value by providing more specific and effective products at a lower cost and without the harmful side effects generally attributed to the lack of biological specificity in the preceding generation of such materials. It is recognized, however, that the use of these new products must be monitored and adequate safeguards be put in place through government regulation.

It is anticipated that plants and plant cells will eventually be designed to produce predominantly single complex chemicals. Because of the rising cost of petroleum-based insecticides and the adverse effect of many of these on the environment, more highly specific biological control agents will be produced. The use of pathogenic insect viruses is increasingly being explored.

The production of new and existing pharmaceuticals by biotechnological techniques, already begun in other countries, is now established in Canada. Canadian pharmaceutical industry research and development has expanded significantly since the passage of Bill C-22 in 1988, which amended the patent law and was designed to encourage increased research and development by the Canadian industry on the basis of extended protection of its proprietary of pharmaceutical discoveries.

The development of biotechnology in Canada has made major strides over the last few years. The number of core biotechnology companies has doubled in the last 3 years, from 121 to 224. Industry revenues have increased from $2.7 billion to $8 billion. Financing activity during 1996 reached $1 billion, equal to the total of the previous 5 years combined. Since biotechnology is an enabling technology, its technical as well as economic impact will span the resource industries, research and development companies and those sectors which depend on their products.

The full economic impact has not yet been realized, but analyses by government and departments and financial service companies conclude that this component of the high-technology sector is now a major part of Canada's new economy. Among the commercial applications of biotechnology are modified canola plants with improved growth and resistance properties; the drug 3TC, used in the treatment of AIDS; herbicide-tolerant crops including corn, cotton and potato; synthetic drugs for cancer treatment using light activation; transgenic wheat; and genetically engineered vaccines for cattle. All of these advances have taken place only in the past 4 years. The economic impact of these and other developments is in the billions of dollars.

The national Biotechnology Development Plan is intended to create a climate appropriate for the establishment and growth of various industries. A National Biotechnology Advisory Committee was organized under the Ministry of State for Science and Technology, with the crucial responsibility of co-ordinating and catalysing a nationwide effort.

This committee represents the various sector interests in Canada, and holds regular meetings focusing on problem areas. A number of information networks, with their own newsletters, have been formed in the key sectors and have proved very useful for exchanging information and fostering collaboration. An inventory of biotechnology activities has been published by the Ministry of State for Science and Technology.

The development of biotechnology in Canada is very exciting, paralleling growth in other countries. Biomedical applications, perhaps the most advanced, have already resulted in the organization of a number of new pharmaceutical and diagnostic companies, and in the expansion and extension of university-based research and production institutes. Problem areas have been identified, and attempts are being made, at the academic level, to train more fermentation technologists and biotechnology-oriented business graduates. Some provinces have organized major efforts, with some provincial research agencies taking on a leading role.

In some respects, biotechnology has been the first and prime beneficiary of the federal government's new high-technology policy. This development seems only appropriate as it has been estimated that 25% of world sales will be biotechnology dependent by the year 2000.

Genetic Engineering

Based on recombinant DNA technology, genetic engineering provides the capability to select DNA fragments or genes (from selected organisms or plant and animal cells, or the products of chemical synthesis), join them to other pieces of DNA, and transfer them to an appropriate production host cell. The resultant micro-organisms thereby acquire novel genetic properties that endow them with the ability to create new products or to use and transform new substrates in fermentation-type processes. These techniques are now applied to the genes of plants, animals and humans. The pending introduction of gene therapy could be a major advance in the provision of health care.

Current areas of application include production of hormones (eg, insulin, human growth hormones), regulators of the immune system (eg, interleukons), growth factors, polypeptide drugs, vaccines and antibiotics. In Canada, research capabilities in this field have now extended beyond the universities and federal government laboratories into large pharmaceutical corporations and a growing number of biotechnology companies. Considerable expertise has been developed, but the number of trained researchers remains seriously inadequate.

Industrial Enzymes

Industrial enzymes are increasingly being used by industry and in health-care applications. Traditionally, enzymes from various natural sources have been used in food production in Japan, the US and Europe; no comparable industry has developed in Canada. Now that enzymes are produced microbiologically and by genetic engineering, "tailor-made" products can be expected. Enzyme immobilization is a crucial part of this technology, and the use of BACTERIA, yeast, FUNGI, and plant and animal cells will provide increasingly sophisticated multi-step, multi-enzyme systems. This includes the use of enzymes in organic media.

New and existing products will increasingly be made with enzyme processes. Essential for the scale-up and automation of such processes is the development of biosensors and optimized computer control of bioreactors and the associated downstream processing equipment. The application of such physics/engineering technologies in the biological domain represents a breakthrough. The development of nano-machines, ultra-micro-machined devices capable of performing biochemical analysis, is expected to lead to the creation of diagnostic, therapeutic and production tools of unprecedented power.

Cell Fusion

Cell fusion techniques have opened up new opportunities in agriculture, forestry and health-care products. In agriculture and forestry, cell fusion can produce hybrid plants exhibiting faster growth, enhanced atmospheric nitrogen-fixing capabilities, and greater resistance to disease, chemical herbicides and climatic factors.Canada's considerable economic dependence on the agriculture and forest industries should make the application of these techniques a high priority. Other hybrid cell techniques result in the production of monoclonal (ie, derived from a single cell) antibodies, used to produce more specific diagnostic reagents, to treat patients with autoimmune reactions, in the targeting and immunotherapy of cancer and for more effective industrial purification of a variety of products.

Plant Cell Culture

Plants have always been a rich source of medicinal agents, and the development of techniques for culturing plant cells in vitro makes possible the production of a wide variety of pharmaceutical products (see PHARMACY). The NRC's Plant Biotechnology Institute in Saskatoon possesses world-class expertise in plant cell culture.

Biological Process and Systems Engineering

The very nature of biological or microbiological products and processes requires special handling techniques and procedures. Specialized bioprocess and engineering systems are therefore central to eventual commercialization. The former paucity of large-scale biotechnology exploitation in Canada has led to a serious shortage of process and bio-engineering expertise. The 1981 Federal Task Force stated that development of such expertise was urgent, and the provision of training represents one of the major activities at the NRC's Biotechnology Institute in Montréal and the Alberta Research Council in Edmonton.