Manipulating life

ONCE scientists learnt that the complexity of life is determined by a single molecule-the deoxyribonucleic acid (DNA) molecule-they have been striving to unravel its structure and molecule carries the code of life in the from of millions of genes.

A lot of scientific effort worldwide is focused on genes. Genetic manipulations have astonishing possibilities -- from finding a cure to diseases such as cancer to enhancing crop production for an increasing population.

Genetic signals
Now that the location of several genes in a cell"s nucleus is known, a major goal of molecular biologists and biochemists is to understand the signals that activate specific genes to respond to stimuli both from within the cells and from outside the body.

The complex mechanisms that stimulate genes to synthesise proteins were discussed at a marathon congress -- the 16th meeting of the International Union of Biochemists and Molecular Biologists -- held in New Delhi recently.

Nobel laureate Edwin Krebs from the University of Washington in Seattle said that a simple on-off switch, much like those used in electronic circuits and microprocessors, controls several life processes such as protein synthesis, metabolism and infection-fighting. Often, a phosphate unit acts as a switch; its addition or removal from a molecule decides the nature of the signal. For instance, the breakdown or conservation of glycogen -- a form in which energy-providing carbohydrates are stored in the body -- is governed by a series of chemical reactions, which use the phosphate mechanism.

Inder Verma from the Salk Institute in San Diego elucidated how certain genes, common to plants such as yeast and found also in fruit flies, are turned on in a cell, making it grow. He showed that when genes are switched on incorrectly, by proteins called onco-proteins, uncontrolled growth of cells results, leading to cancer.

Nam Hai Chua from Singapore, who is the Andrew De Mellon professor at the Rockefeller University in the US, took the instance of how plants respond to light. He explained that a molecular switch called phytochrome in plant cells is turned on by light. Once the switch is on, a series of elaborate steps lead to the production of chloroplasts -- the light-harvesting powerhouses found in plant cells.

Chua"s work reveals that this pathway is reciprocally controlled by another series of chemical reactions which lead to the formation of anthocyanin -- the red pigment found in petals and in young leaves, which offers protection from intense light. When the leaves mature, the anthocyanin production pathway is turned off; phytochrome is then switched on in response to light, and the leaves turn green.

Gene therapy
Another area of molecular biology that came up for discussion at the meeting, organised by the Society for Biological Chemists and the Indian National Science Academy, was gene therapy. As evidence for gene defects being responsible for ailments such as cystic fibrosis, Alzheimer"s and Parkinson"s disease, and even cancer, comes to light, researchers are exploring the possibility of manipulating genes to correct these flaws.

Explains Verma, who has pioneered a method of introducing new corrective genes into cancerous cells using viruses, "In Parkinson"s, for example, we can introduce a particular gene that can produce a certain chemical in the brain, which is necessary to correct Parkinson"s disease." Nearly 100 human trials involving gene therapy are underway and the majority are on cancer.

Kunio Yagi of Japan pointed out that for gene therapy to work, the new genes must be transferred to target cells without harming them. Yagi elaborated a technique that he has developed, in which genes are packed within vesicles called liposomes which can home onto the target cells. He successfully entrapped the gene for interferon -- an accomplished cancer warrior that is normally produced in the body in minute quantities -- in liposomes and injected them into cancer-affected brain cells. The gene then produced interferon in the brain cancer cells, knocking them out. He says he has now sought permission to undertake clinical trials.

Possible cancer vaccine
A possible cancer vaccine based on gene therapy was suggested by M L Birnstiel of the Vienna-based Research Institute of Molecular Pathology. He said that cancerous cells are not recognised as foreign by the body"s immune system and so are left to multiply unchecked. But the immune response of the body to these aberrant cells can be enhanced by a substance called interleukin-2 which activates dormant immune cells. Using interleukin-2, Birnstiel has successfully generated what he calls tumour vaccines which gave at least 80 per cent of the mice, whose cells were manipulated, life-long immunity against cancer.

While gene therapy is being tried on several patients, scientists are trying to improve methods to transfer genes into cells. Apart from liposomes, scientists like Verma, for example, are trying to use modified viruses to incorporate genes into cancer cells, some are trying to inject the gene into the cell, while others are altering the permeability of the cell membrane using electricity.

Efforts were reported where the patients cells are removed, engineered and reinserted, but experts point out that these patient specific procedures are fairly expensive and difficult. Other experts like Birnstiel pointed out that gene therapy is still at in the "stone age", and Verma conceded that though there are risks involved, "any manipulation will have risks".

Crop yields
But by far the most tangible results in genetic manipulation are seen in plants and microorganisms. According to experts such as Indra Vasil from the --- and one of the first scientists to genetically transform wheat plants, with an increasing world population and little additional area available to grow food crops, biotechnology could help increase crop yields.

Several Indian scientists from different parts of the country put up posters at the meeting and explained informally their attempts to incorporate different genes in crops and other plants including trees.

Scientists at the meeting also discussed the latest advances in AIDS treatment, contraceptives and new drugs.