NIEHS Fact Sheet #2 - How - 8/96
HOW do scientists study the effects of environmental factors -- such as man-made and natural substances, and radiation -- on human health?
Headlines such as, 'PEOPLE IN POLLUTED CITIES HAVE MORE BREATHING DIFFICULTIES' are familiar to most of us. They are likely to be about a study of the occurrence of diseases in people who have been exposed to a natural or man-made factor in the environment.
That kind of work is called epidemiology. It is the best known, best understood and most accepted tool of the environmental health sciences. It is the type of research that most health regulations are based on. The linking of cigarette smoke to lung cancer (and then to many other conditions) was carried out, in large part, by epidemiology. To show that link, which seems so obvious today, researchers not only had to compare smokers with non-smokers over many years, they had to rule out many other exposures these people might have had.
Epidemiology is the way scientists found that caffeine decreases a woman's fertility and that exercise reduces the risk of heart attacks. Epidemiologists may use questionnaires and other polling techniques -- or biological tests of people. A sophisticated combination of these techniques recently helped NIEHS show that many fetuses develop and die without a woman knowing she's been pregnant, and that women are fertile on the day of ovulation and several days before, not after.
Valuable as it is, epidemiology has limits: It is hard to separate and sort out exposures -- or to document them years later when a disease develops. Small differences in exposures or disease rates may not be detected. Also, since diseases such as cancer may not appear for many years, reliance on epidemiologic techniques means that people may have to be exposed for a generation or more before a problem is recognized.
Thus, another important tool, in use for the past 60 years, has been the testing of substances in animals. Scientists call these screening tests animal assays. In a typical assay, mice and rats are exposed to various levels of a substance for two years and checked for changes in their development: Are there more cancers than normal -- or cancers not usually found in these animals? Are there changes in the exposed animals' reproductive, cardiovascular, immune or nervous systems?
Some people doubt the results -- doubting, in effect, that they are enough like mice and rats to be hurt by the same materials. In fact, mice and men share many genetic characteristics, and most substances known to cause cancer in humans -- aflatoxin, asbestos, benzene and radon, among them -- also cause cancer in animals.
The National Toxicology Program, headquartered at NIEHS, has been working on screening methods that use fewer animals and take less time and money. One alternative would use a special strain of mice that has been genetically altered. That is, scientists have added a human or other foreign gene to the mouse line or have eliminated or suppressed the activity of a gene that controls a certain function. Such a line of mice could react to lower dosages of a carcinogen or poison in a shorter time.
In addition, researchers are working on ways to help predict the harmful effects of chemicals using cell cultures and suspensions, microorganisms, crustaceans, certain strains of small fish and mathematical and computer models. NIEHS scientists are working with industry and other research institutes to establish standards and guidelines for the use of these new methods for research, and for regulatory and public health purposes.
One of the newest and most exciting research fields is the search for basic biological mechanisms. Scientists, in this case, are not looking at people or mice, but at our common building blocks -- cells, molecules and genes. The scientists are using advanced techniques, procedures, equipment and computer simulations to see, or at least infer, what happens when a molecule of a toxin or carcinogen assaults a cell or gene.
Scientists are studying the damage to our DNA, the chemical strand inside the nucleus of every cell that determines our own and other species' inherited characteristics. When DNA is damaged, a protein in the body sometimes ordinarily detects it -- kind of like "spell check" finding a misspelling in a computer document -- so it can be repaired. But sometimes this repair fails or is poorly done. The outcome of this repair process may mean the difference between health and chronic illness. Some of these failures may mean that genetic defects are passed on to subsequent generations.
Researchers are also looking at the rate at which the body's cells divide and the way in which they communicate with one another. Many of these functions are controlled by special signaling molecules called G-proteins, discovered by Nobel laureate and NIEHS scientist Martin Rodbell. When these G-proteins are damaged, either through genetic defects or environmental influences, errors in the signaling process can occur. This can lead to changes in the control of cell growth and other important functions and result in cancer and other diseases.
While epidemiology dates back to a description of the spread of plague in the 1600s, the environmental health sciences are also on the cutting edge of today's science. By combining old techniques with new, scientists can better determine the links between environmental exposures and human disease -- links that can help medicine prevent many diseases and premature deaths.
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NIEHS Fact Sheet #2 - How - 8/96
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