You go to a doctor and he gives you a prescription. You take it to a drug store and you get some pills. You take the pills and you start feeling better.
It's an oft-repeated procedure and one that we often take for granted. Yet, behind every one of the drugs dispensed by modern medicine lies thousands and thousands of tests and studies. Each little pill represents its own miracle of modern science. And new strides are being made all the time.We are, in fact, on the verge of a second revolution of pharmaceutical innovation, akin to the discovery of antibiotics in the 1940s, says Frank E. Young, commissioner of the Food and Drug Administration. "Medicine is making great strides in a number of areas, and we have more to offer patients than ever before. Over the past two years, biotechnology has prompted breakthroughs in major areas."
Still, he says, the process of developing new drugs is not very well understood by most people - at a time when that understanding is increasingly important. "I believe the public now, more than ever before, needs a clear understanding of how new drugs are developed and approved. Any one of us, at some time, may be in need of a new therapy to cure an ailment or improve the quality of our lives. Moreover, the terrible AIDS epidemic has brought a new urgency to thousands of Americans who, tragically, simply do not have long to wait for medical discoveries."
As consumers - and as patients or potential patients - we need to understand what the different steps in drug development are, why they are necessary, and what the FDA, the pharmaceutical industry and health professionals are doing to make those steps as short as possible, says Young.
THE RESEARCH: There is no standard way new drugs are developed; each of the 2,400 compounds currently sold in the United States had a different research path. But there are some similarities.
Most of the research is being done at pharmaceutical companies around the country, and often they are looking for a drug for a specific use. At other times, researchers simply pursue promising lines of research.
Disease processes are extremely complex. To intervene in the process, scientists must have a clear understanding of all the component parts and target the drug reaction to a specific interval.
As a case in point, take the development of a new cholesterol-lowering drug. Cholesterol is a wax-like substance found naturally in the body, but too much cholesterol, either naturally or in the diet, can cause it to build up on the inside walls of blood vessels, thus clogging arteries that deliver blood, oxygen and nutrients to vital parts of the body.
There have been few drugs that effectively cut cholesterol levels without either toxic or unpleasant side effects. Others acted too late in the process by which the body makes cholesterol to do much good.
After decades of study of the cholesterol-making process, researchers identified more than 20 biochemical reactions necessary for the body to make cholesterol, and found enzymes that were required at each step to turn one chemical into the next one in the chain.
So, what was needed was a step where interference by a drug would effectively lower cholesterol production. By the 1970s, scientists had a possibility. They had isolated a chemical, mevalonic acid, that was an early link in the cholesterol chain and an enzyme called HMG-CoA reductase that produced mevalonic acid. If they could come up with a compound that inhibited production of the enzyme or prevented cells from correctly using it, they might have a way to lower cholesterol production.
Researchers have several options for continuing study. They can use computers to simulate an enzyme or other drug target and design chemical structures that would work against it. The computer can narrow the field, although any compounds based on a computer still need to be tested in a biological system to see if they work.
Another approach involves testing compounds made naturally by microscopic organisms such as fungi, mold, viruses and so forth. It is not unusual to test as many as 100,000 different microorganism fermentation broths to see if any of the compounds have a desirable effect.
In the search for the new cholesterol drug, researchers found a fungus that inhibited the HMG-CoA reductase enzyme in a a test tube.
The next step is to test it in actual biological systems. Scientists need to know what effects the drug has on living systems - and what effects the biological systems have on the drug.
If animal studies prove a drug has promise, it may then be approved for human testing.
THE ROLE OF THE FDA: The FDA becomes involved when a drug company has completed its testing in animals and is ready to test a drug on humans. FDA physicians and scientists review test results to determine whether the drug is safe enough to test in humans and, if so, whether it can be sold to consumers. Some animal testing may continue after human testing begins to determine whether long-term use of a drug may cause cancer or birth defects. And if human tests turn up unexpected results, more animal data may be required.
There is a common misconception that the FDA is responsible for testing drugs before they're approved for sale. It is the drug companies that perform the tests, and the FDA that monitors results.