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'Chasing Ehrlich's dream: the quest for magic bullets'

by Sandip K Basu,
National Institute of Immunology

Largely forgotten today, Dr Yellapragada SubbaRow was greatly admired as the 'Wizard of Wonder Drugs' such as Aureomycin, DEC, folic acid, and methotrexate. Born an Indian, Dr SubbaRow remained an Indian throughout his life and died in 1948 at the age of 53. He could not be honoured appropriately in his lifetime, but “because he lived you may be alive and are well today. Because he lived you may live longer". I sincerely feel that the only way we can honour this great Indian is to emulate his work that ensured equitable and affordable healthcare for over half a century to the poor and the rich alike all over the world.

In the value system of human society, the priorities are health followed by wealth followed by wisdom. This quest for good health and the urge to avoid or get over illness has driven mankind over millennia to flock towards medicine men. Modern medicine based on systematic scientific studies about the causalities of various disease processes is, however, only a little over 100 years old. Modern medical practices combining improved sanitation, immunization and the use of medicinal substances of natural or synthetic origins has drastically reduced morbidity and mortality from infectious agents. However, emergence of drug resistant pathogens and new diseases such as AIDS in recent years rudely reminds us that the war against microbes is hardly over.

Healthcare in the 21st Century crucially depends on our proficiency in the sunrise technology of molecular medicine. The edifice of molecular medicine can only be built on a firm bedrock of competent and innovative new biology research. I would like to pay homage to Dr SubbaRow by citing some examples of our humble efforts in this direction to break new grounds.

Ours has been the best of times globally because this is the first century in which mankind had some respite from the constant fear of premature death from diseases. Life expectancy has risen from about 30 years at the end of the 19th century to about 80 years in most developed countries. Even an Indian can expect to live to be about 64 today whereas it was about 33 only fifty years ago.

Ours could also turn out to be the worst of times. The deluge of new and re-emerging diseases, drug-resistant microbes and the epidemic surge of AIDS pose hazards of calamitous dimension to public health. At development costs of over $500 million and 10­-15 gestation years per new drug, even chemotherapy is fast becoming unaffordable. Public trust in modern medicine is fast eroding with the spiralling rise in healthcare costs and the resultant inequity in healthcare delivery is aggravating social discord. We are living in dubious and dangerous times indeed.

Shifting Paradigms in Health Care in Century 21. As the lifestyles in the poor nations improve, a demographic transition in the disease pattern is sure to happen in our parts of the world as well. With the increased life span and an ageing population, the major goals of medicine in the 21st century are control of cancer, cardiovascular ailments, autoimmune diseases, and behavioural disorders. As the molecular defects underlying pathological conditions are elucidated, medicine in the new century will shift to an informational paradigm that will emphasise diagnosis and prevention rather than expensive therapy. An era of "predictive medicine" will emerge that will permit assessment of the risk of an individual to contract a specific disease so that many of such risks would be countered by preventive measures, counselling, lifestyle changes, and so on.

There is robust optimism that new technologies for equitable healthcare will emerge in Century 21 from the profound molecular insights into life processes that new biology provides.

New biology is the outcome of the convergence since the 1940's of the three major streams of biology: biochernistry concerned with the isolation and chemical characterization of cell substances, cell biology exploring the subcellular components of the cell, how they relate to each other and to the intact cell, and genetics dealing with the inheritance of characters by whole animals or plants. New biology seeks molecular explanations for the many ­splendoured beauty and aberrations of life, how it perpetuates and evolves, and how it originated.

The powerful molecular approaches of new biology for studying disease processes has spawned a new biopharmaceutical industry that specializes in studying mechanisms of diseases and applies that knowledge to their diagnosis, prevention and treatment. The triumphant march of the biopharmaceutical industry is reflected in the large number of new products that are approved or are in trial.

Chimeric toxin. Some of the proteins under development have no precedent in nature: they are engineered as combinations of certain domains from several proteins. For instance, Dr J.K Batra and his colleagues at NII are using gene fusion techniques to develop a molecule in which the EGF receptor-recognizing domain of the TGF molecule is fused to a fungal toxin called restrictocin that inhibits protein synthesis in animal cells. This hybrid protein selectively destroys breast and lung cancer cells that overexpress EGF receptors. For killing other types of tumour cells, which overexpress transferrin receptors, they have engineered a molecule containing the transferrin-receptor-binding domain of an antibody and a potent fungal toxin.

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(c) Evelyn Publishers, This Website is dedicated to Dr Yellapragada SubbaRow whose contribution to human well being is unparalled