Genetic voodoo gains ground

  • 14/10/1993

Rapid developments in human gene cloning and efficient gene-transfer technologies have opened up the possibility, in a sense, of producing transgenic humans. In the past four years, researchers have cloned and sequenced many defective genes that cause diseases, including those responsible for several types of muscular dystrophy and most recently, the gene for Huntington's disease -- a fatal neurodegenerative disease. Scientists are now looking for ways to repair defective genes and put them back into cells.

Though several problems remain, less than three years after a ground-breaking experiment carried out by French Anderson and colleagues at the National Institutes of Health in Maryland, gene therapy is gaining supporters. Scientists in Maryland took the defective white blood cells of a young girl with adenosine deaminase deficiency (an inherited condition where people have a weakened immune system) and corrected them genetically and replaced them. More recently, five-day-old Andrew Gobea, who was suffering from bubble bay disease, a usually fatal immune system defect, became the first newborn to undergo gene therapy. Surgeons at a Los Angeles hospital injected him with gene altered cells obtained from his mother's placental blood to cure the disease.

Several companies are trying to develop gene therapies for lung cancer, breast cancer and cystic fibrosis. Today, at least 11 gene therapy protocols have been approved in USA and Europe. Bob Williamson of St Mary's Hospital Medical School in London is optimistic about gene therapy, especially to remedy multi-factorial diseases such as cancer and heart disease, which are caused not only by genes, but also by factors like the environment. But he cautions the euphoria about this new treatment should not lead scientists to neglect the development of new chemical drugs, using traditional research routes.

Jurgen Drews of Hoffmann-La Roche reckons if gene therapy becomes successful for even just those diseases now identified as experimental targets, the impact on drug therapy would be substantial, replacing today's equivalent of $12 billion in drug sales.

Meanwhile, in another kind of genetic engineering, genes taken from harmful bacteria and viruses are moved into cell cultures where they produce antigens -- substances that are recognised as foreign by the human body. "These antigens can be made into vaccines," says Kanuri Rao, a scientist at UNIDO's International Centre for Genetic Engineering and Biotechnology in New Delhi, who is working on a recombinant hepatitis vaccine. The antigens activate the body's immune system in the same manner as when it exposed to invading viruses carrying similar antigens. As yet, these vaccines, known as sub-unit vaccines, are not very effective because the human body's immune response to them is weak.

In an alternative approach, a live vector -- a harmless bacteria or virus -- is engineered so that it is incapable of causing disease and to it are added genes that code for antigens of a particular disease-causing pathogen. The advantage of this approach is that the vector is immediately recognised as foreign and is a more effective primer.

A superior vaccine vector candidate is the vaccinia virus -- the cow pox virus -- which was used to eradicate small pox. However, though several vaccines using vaccinia are being developed, none has been okayed because a number of people react adversely to vaccinia. Moreover, scientists fear vaccinia may take on a virulent pox virus form, reintroducing an uncontrollable scourge like small pox. Tilahun Daniels Yilma, professor of veterinary microbiology and immunology at the University of California who developed a vaccinia-based recombinant vaccine against rinderpest -- a disease that afflicts cattle in India and Africa -- was recently denied permission by the department of biotechnology to undertake trials of the vaccine in India.

The hepatitis B vaccine was the first recombinant DNA vaccine to come into the market and though several others are being developed, they are yet to hit the market. The search for a vaccine against the human immuno-deficiency virus that causes AIDS also involves the use of recombinant DNA. Vaccines to prevent tropical parasitic diseases like malaria and schistosomiasis are also being developed in different parts of the world.

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