N.e.w  D.r.u.g.s  B.y   D.e.s.i.g.n

       The search for new drugs has traditionally relied on trial and error. A chemist might synthesize a new molecule, which a pharmacologist would screen for evidence of useful biological action. Alternatively, a particular molecule might be known to have an action that doctors realize is useful; the chemists could then synthesize variants in the hope of making a more active version. Although this method has yielded large numbers of useful drugs, it is wasteful. Much better would be to design drugs for specific purposes. And this has now become a reality.

    Talk to anyone in the pharmaceutical industry, and you'll soon discover that genetics is the biggest thing to hit drug research since a penicillin mold floated into Alexander Fleming's pert dish. Sure, scientists have long known genes play a role in almost every ailment from Alzheimer's to yellow fever. But it is only in the past few years that they've learned how to use that information to identify a multitude of new targets and pathways for drug design.

  Drugs by design

    Geneticists estimate that there are 2,000 to 5,000 genes that may lead to various diseases.That means there will be many, many more possibilities of research than the entire pharmaceutical industry could possibly hope to investigate over the next 20 years. Each company has a different strategy for exploiting that bonanza, but they all agree on a few key points:

--	Drugs will be safer, more powerful and more selective than before.
--	Doctors will be able to consult your genetic profile to determine ahead of time whether you are more likely to respond to one type of medication or another.
--	Computers and other digital technologies are going to play a much bigger role in evaluating new research and determining how patients should be treated.

    Let us preview a little history to get a better understanding of the future. Just a few decades ago--the process of discovering a new drug was a lot like shooting a quiver of arrows into the air and then running around to see what they hit. In this way though occasionally scientists did get lucky, most of their efforts were wasted.

    This started to improve in the 1970s and early '80s as researchers used recombinant-DNA technology to mix and match bits and pieces of hereditary material. Suddenly they discovered genes directing the construction of RNA molecules, which in turn assembled proteins, enzymes and other biological molecules. Instead of shooting their research arrows into the air, drug companies could aim at defined targets. For example, the scientists focused on the serotonin receptors in the brain and developed Prozac for the treatment of depression.  Targeting histamine receptors in the stomach produced Tagamet and then Zantac to relieve acid indigestion.

Production of messenger RNA from DNA

    By the 90s, 500 different targets have been identified. Thanks to the Human Genome Project, researchers expect to identify another 500 in just the next few years. Soon there will be more new targets than even the largest companies can handle. The problem then will be to assign different priorities to the targets.

    One approach is to focus on the diseases that affect the most people--those associated with aging, and to do it by aiming for the targets that are the most accessible. That generally means designing a drug that affects the proteins and enzymes that exists on a cell's surface or in its cytoplasm, not the genes that code for those proteins and enzymes, which are usually found in the protective nucleus of the cell.

    Human Chromosome Preparation

    While drug companies are focusing on developing chemical compounds, other scientists prefers to develop it from the biological side--hormones, proteins and other substances. Examples include interferon, the clot buster tPA and the new breast-cancer drug Herceptin.

    Some scientists even want to go a step further. They want to move one step closer to the gene by targeting the RNA molecules that transfer information from genes to proteins. And they have the perfect molecular tool with which to do it. By synthesizing strands of DNA that are the mirror image of the RNA they wish to block, researchers can produce a drug that is most specific in any case. Because it interrupts the "sense" that the cell is trying to make of the RNA molecule, the new technology is called 'anti-sense'.

    There are still many things to be worked out at this stage. For example, the body's own immune system often attacks the anti-sense DNA, mistaking it as a potentially harmful virus. Many cells in the body don't allow the anti-sense molecules to cross their membranes.  Now, after a few years' of the scientists' hard work,  a few anti-sense compounds are starting to show promise. Among them is a drug called Vitravene, which was approved by the Food and Drug Administration in August and is used to prevent blindness in AIDS patients infected with cytomegalovirus.

   Genes don't just tell you how to make drugs. They can also tell you whom to treat.

    The pharmacology of the future will also make greater use of natural chemicals such as interferon and interleukin. By isolating these materials, identifying their roles in the life and control of cells, and then synthesizing them in quantity, it will be possible to manipulate the body's physiology in ways used by the body itself.

  Fighting AIDS: Scientists seek new drug design route