Medical Applications of Biotechnology

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       The applications of current day biotechnology are too many to be discussed here. Only those relevant to health care are outlined below, in addition to those already mentioned.

4  PRODUCTION OF ANTIBIOTICS

        The world trade in antibiotics alone is about US$ 15 billion per annum and represents a significant fraction of the pharmaceutical industry’s revenues. These substances are very varied in chemical structure and mainly act to inhibit the growth of bacteria. Economically the most important groups of antibiotics are the penicillins, cephalosporins and tetracyclines. Other major groups include the polyene macrolides, streptomycins, erythromycins, rifamycins, groups bleomycins and anthracyclines, which affect various aspects of cellular metabolism ranging from DNA replication to protein synthesis. There are also some natural antifungal and antiparasitic compounds which are, in general, grouped with the antibacterials.

Antibiotics are also used widely in biochemical and biomedical research. It is now an attractive proposition to produce effective antimicrobial agents from higher plants, through biotechnology.

4   PRODUCTION OF VACCINES

       Vaccine production can be hazardous if highly pathogenic organisms must be grown it culture and then killed to provide a source of antigens. It has been possible to clone the genes coding for some viral antigens and to produce just these proteins in genetically engineered bacteria. Such vaccines are safer and easier to produce and, if the cloned antigen is well chosen and correctly expressed, should be as effective.

       Transgenic systems were once thought useless in the area of immunology. Now plants are known to express and accumulate complex secretory antibodies. Consequently, vaccine production through transgenic plants is now a reality (Suprasanna et al., 1997).

4  PRODUCTION OF MONOCLONAL ANTIBODIES

       It is now possible to use monoclonal antibodies to confer immunity. The ideal product for therapeutic use would be human antibodies but, at present, these can only be produced from human hybridoma cell lines, most of which are not very stable. Mouse antibodies may themselves cause an allergic response in humans but probably only after they have been administered several times. Therefore, mouse monoclonals will probably be used in life-threatening situations but human antibodies will be needed for prophylactic treatment. Cloning and expressing antibodies (immunoglobulins) in bacteria and yeast has been reported a long time ago, and plants doing the same, in recent times. Such work provides a very neat link between genetic engineering and monoclonal antibodies which will enable large scale production to be undertaken. It may also overcome many of the technical problems of hybridoma lines.

4    PRODUCTION OF THERAPEUTIC AGENTS IN BIOREACTORS

       An important area of plant biotechnology is the in vitro culture of plant cells. Plant cells carry out many complex metabolic processes which yield useful products such as rubber and the pain-killing opioid alkaloids. These cultured plant cells provide new sources of pharmaceutical and chemical substances.

      Over 80 per cent of natural compounds are of plant origin. Many of these compounds are of importance in industry, agriculture and medicine. Most of these compounds cannot be either synthesised artificially or the products of such synthesis are inferior to the natural product terms of activity, or by cost-effectiveness. Under these situations cell/tissue culture techniques hold immense promise.

       Bioreactors offer a great hope for the large scale synthesis of therapeutically active compounds in medicinal plants. Since the biosynthetic efficiency of populations vary, one should select a high yielding variety as a starting material. While theoretically any part of the plant may be chosen for use, a part with actively dividing cells such as the meristem is to be preferred. It requires repeated subculturing to obtain a friable callus, from which individual cells could be easily isolated. The callus forms the basis for the preparation of cell suspensions. High yielding cell lines are chosen from different crops of cell suspensions. One should keep track of the quantity of the desired phytochemical compound from the starting plant, explant, callus and the product recovered from the suspension cultures. Once a promising cell line is isolated, and the suspension culture process is successful, the bioreactor processes may be contemplated with a prototype small-scale reactor system. The fundamental requirement in all this is a good yield of the compound, compared cost effectively to the natural synthesis by the plants.

       A wide variety of compounds have been shown to be produced in shoot, callus (Table 1), or cell suspension cultures (Table 2) at levels equal to or higher than the levels in the intact plant sources (Dodds and Roberts, 1995; Brodelius, 1988; Charlwood and Charlwood, 1991). That phytochemical compounds belonging to almost every class have been produced in cell cultures and that these compounds are therapeutically important, indicates that, at least theoretically, any chemical compound can be produced in suspension cultures (Table 2), provided the right conditions. The compounds so far produced are industrially or therapeutically important and show great promise for bioreactor processing.

       Ginseng root tissue cultures in a 20 tonne bioreactor produced 500 mg/L/day, of the saponin which is considered as a very good yield (Charlwood and Charlwood, 1991). Using a bioreactor of 20 litre capacity, successful results have been obtained in culturing cells of Catharanthus roseus, Artemisia annua, Nothopodytes foetida and Digitalis lanata, at the Biotechnology division of the Bhabha Atomic Research Centre (BARC) at Bombay. The BARC has recently designed a 100 litre bioreactor.

TABLE 1

Secondary metabolites produced in callus cultures at levels equal to or exceeding those in the intact plants

Data from Charlwood and Charlwood, 1991.

TABLE 2

Secondary metabolites produced in cell cultures at levels equal to or exceeding those in the intact plants

Data from Barz and Ellis, 1981; Dodds and Roberts, 1995; Brodelius, 1988; Charlwood and Charlwood, 1991.

4    MICROPROPAGATION OF MEDICINAL PLANTS

        Some plant species are very difficult to propagate by seed. In such cases, in vitro production of clones of single cells or tissue explants from which whole plants can be raised in a very large number, is a major area of research. Particular success in this area has been obtained in orchids, banana and oil palms. A number of medicinally important species have been successfully experimented for mass production by micropropagation, the latest being Gloriosa superba, a source of many alkaloids (Sivakumar and Krishna Murthy, 2000).

        If a particular plant variety is a high level chemical line, it could be produced in large numbers by micropropagation yet maintaining its quality, which is difficult under conventional cultivation methods. A number of medicinally important species of plants are under threat for various reasons. They need to be protected and conserved. Some other species are in great demand in industry and medicine. Conventional cultivation methods are both slow and inadequate to meet the demand. Micorpropagation is the answer for these problems too (Patil and Jayanthi, 1997).

       The content of azadirachtin in seeds of micropropagated neem plants in relation to their mother tree compared very favourably (Venkateswarlu and Mukhopadhyaye,1999). Such findings point out to the usefulness of micropropagation, but all species do not respond in the same manner.