Indeed, there are immense possibilities of new industrial applications and increase in the productivity of microbes, plants and animals already in useToday, many developed nations are harnessing biotechnology for deriving benefits in sectors such as food and agriculture, chemicals, drugs and pharmaceuticals, energy and environment.

Fortunately, even a developing country like India offers multiple opportunities in areas of sustainable development in agriculture production, health care and environment protection.

Under the government's pragmatic and farsighted policy framework envisaging transfer and absorption of resources and technology on congenial terms and promoting dedicated research and application, biotechnology holds out a promising future. Vaccines are the most powerful tools to protect againstdisease.

They safeguard millions of children and adults from life-threatening illnesses, including polio, tetanus, diphtheria, whooping cough, yellow fever, Japanese encephalitis, measles, Hepatitis B, meningitis and influenza.Thanks to vaccines, smallpox disease has been eliminated from the planet. Vaccines are also the most economical intervention, offering a sensible approach to reducing health care costs associated with infectious disease.The Indian Expanded Programme of Immunization (EPI) has to cater to about 23 million new borns against childhood diseases and an equal number of pregnant women against tetanus, which calls for making available in very large quantities of vaccines. However, abundant capacities have already been created in the country for the production of vaccines against Tetanus, Diphtheria, Pertussis (and combinations thereof like DPT and DT), BCG and measles.

Sheep brain derived as well as chick embryo cell culture based rabies vaccines, yellow fever, Japanese encephalitisvaccines, inactivated cholera and typhoid vaccines are also being produced locally.

In addition to active vaccines sensitized equine anti-sera against tetanus, gas gangrene, rabies and snake venom are also produced locally. A manufacturing unit with an annual production capacity of 100 million doses of oral polio vaccine was set up by the central government at Bulandshah (UP) through technology consultancy with Russia and the unit was commissioned in 1994.

Currently vaccines against FMD, anthrax, BQ, MCC, and enterotoximia, rinderpest, rabies, and sheep pox are being produced in the country in abundant quantities. The poultry industry is also developing fast in the country.

Several viral vaccines for poultry like La Sota, infectious bronchitis, fowl pox, New Castle disease, Ranikhet disease, Marek's disease, etc are being produced in large quantities. The total production of animal and poultry vaccines amounts to in excess of Rs 500 million and this is expected to grow at the rate of about 10 per centper annum in quantitative terms during the next five to eight years.

Genetically engineered as well as human plasma derived hepatitis B vaccines are being developed and marketed in the country by: recombinant DNA derived vaccines : EngerixB ( Smith Kline), Enivac HB (Panacea), Shanvac (Shanta Biotech) and plasma derived : Hepavax (VHB Pharma).

Similarly human diploid cell culture based rabies vaccine and improved cell culture vaccines against measles, mumps and rubella (MMR), and influenza are beng imported and consumed. The human vaccine market, to a large extent, is controlled by the private sector, with very few public sector companies like the Haffkine Institute, Indian Immunologicals, etc.

A number of government aided and private research institutes are engaged in carrying out research in the development of vaccines in India. Institutes like the National Institute of Immunology, the National Dairy Development Board, Center for Cellular and Molecular Biology, are actively interacting with privateindustry by transferring technology for vaccine production.The Government of India set up the Department of Biotechnology over a decade and a half ago, after identifying two thrust areas of biotechnology namely: agricultural biotechnology and vaccine development. Yet, a large chunk of the Indian vaccine requirement is still supplied by imports or by multinational pharmaceutical giants based in India.

The current imports of these vaccines vary between 50,000 and 400,000 doses per annum, and are considered low primarily due to their higher unit costs. Several other vaccines like attenuated oral as well as Vi antigen based injectable typhoid vaccine, H influenza type B, meningitis and varicella (chicken pox) vaccines are also required in the country in sizable quantities although these are not yet available.

During the year 1993, the turnover of human vaccines in the country at manufacturer's level was estimated to be of the order of Rs 1035 million for active vaccines and about Rs 230 million in terms ofsensitized equine anti-sera.

The total turnover of sera and vaccines used for human ailments is Rs 1265 million. The vaccine market is growing at the rate of 8-10 per cent annually in quantitative terms with the equine anti-sera market being almost static.A classical case of market forces governing the costs of even life- saving vaccines is seen in the price war of the Hepatitis B vaccine.

In the present scenario, with more than five companies in the fray, the prices of this crucial vaccine have seen a sharp decline in the last couple of years.

The main beneficiary of this saga is the common man who can now afford to immunize his children against this deadly disease.

There are opportunities for the setting up of basic production facilities for MMR, measles, cell cultured rabies vaccines, recombinant Hepatitis vaccine, oral and injectable typhoid (Vi antigen based) and other vaccines as the demand is increasing and the current production base is not sufficient for most of these vaccines.

Besides, thesale of these products is primarily through private consumption by physicians who exhibit ability to pay higher prices.

Vaccines remain among the most powerful tools we have for disease prevention. Advances in biotechnology have ushered in a new era in vaccine development. Through genetic engineering, scientists can isolate specific genes and insert them into the DNA of certain microbes or mammalian cells grown in the laboratory, which become living factories, mass producing the desired antigen.

Then, using another product of biotechnology, a monoclonal antibody that recognizes the antigen, researchers can separate the antigen from all the other material produced by the microbe or cell. This technique has been used to produce safe vaccines that stimulate the human immune system against such organisms as the hepatitis B virus.

In another approach, scientists have inserted genes for desired antigens into the DNA of related but harmless viruses such as the vaccinia virus, a relative of the cowpox virusthat was used in modern smallpox vaccines. When the re-engineered vaccinia virus is inoculated, it stimulates an immune reaction to both the vaccinia and the products of its passenger genes.These have included, in animal experiments, genes from the viruses that cause hepatitis B, influenza, rabies, and AIDS. Scientists similarly are using bacteria such as salmonella as vaccine vectors to carry portions of microbes. Instead of adding a gene, some scientists have snipped a key gene out of an infectious organism.

Thus crippled, the microbe can produce immunity but not disease. This technique has been tried with the cholera bacterium and with herpes simplex virus. DNA vaccines employ a new approach in which genes from disease-causing microbes are isolated and injected directly into a person. Some of these genes enter host cells, which then synthesize the proteins encoded by the injected genes. The foreign proteins elicit an immune response that may protect against subsequent infection by the microbe.A DNAvaccine against AIDS is now being tested in people. A totally different approach to vaccine development lies in chemical synthesis. Once scientists have isolated the gene that encodes an antigen, they are able to determine the precise sequence of amino acids that make up the antigen. They then pinpoint small key areas on the large protein molecule, and assemble it chemical- by- chemical. Wholly synthetic vaccines are being explored for malaria and diarrheal diseases prevalent in developing countries. A vaccine against Type I diabetes (insulin dependent diabetes) is also in the development stage, as the gene responsible for this form of diabetes has been identified, and efforts are on to bring this vaccine in the market in the near future.

The authors work with Biotechnology Resource Centre