The debate over the relative contributions of genetics and environment—"nature versus nurture"—remains unresolved in many fields of study, from education to animal behavior to human disease. Historically, scientists assumed opposing viewpoints, choosing to favor either nature or nurture, rather then exploring the ways in which both play critical and complementary roles. Proponents of "nature," or a person's inborn traits, argued that human characteristics are uniquely and primarily conditioned by genetics, disputing the view of those who asserted that environmental influences and experiences ("nurture") determined differences between individuals and populations.
Genes versus Environment
When researchers analyze the origins of disease, the terms used to describe causation are "genetic" versus "environmental," but the issues are the same as those in the nature-versus-nurture debate. Conditions considered to be primarily genetic are ones in which the presence or absence of genetic mutations determines whether an individual or population will develop a disease, independent of environmental exposures or circumstances. A disease considered to be primarily environmental is one in which people of virtually any genetic background can develop the disease when they are exposed to the specific environmental factors that cause it.
Even the conditions and diseases once believed to be at either end of the continuum—caused by either purely genetic or purely environmental factors—may not be exclusively attributable to one or the other. For example, an automobile accident that results in an injury might be deemed entirely environmentally caused, but many geneticists would contend that risk-taking behaviors such as the propensity to exceed the speed limit are probably genetically mediated. Furthermore, the course and duration of rehabilitation and recovery from an injury or illness is also very likely genetically influenced.
At the other end of the continuum are diseases believed to be predominantly genetic in origin, such as sickle-cell anemia. While this disease does not have an environmental cause, there are environmental triggers that may determine when and how seriously the disease will strike. For example, sickle-cell attacks are more likely when the body has an insufficient supply of oxygen, so people who live at high altitudes or those who engage in intense aerobic exercise may be at increased risk of attacks. There are many more conditions for which the risk of developing the disease is strongly influenced by both genetic and environmental factors. Multiple genes and environmental factors may be involved in causing a given condition and its expression.
Asthma: A Disease with Genetic and
Asthma, a disorder of the lungs and airways that causes wheezing and other breathing problems, is a good example of how genes and the environment can interact to cause diseases. The scientific evidence that asthma had a genetic basis came from studies conducted during the 1970s, 1980s, and 1990s, which found patterns of inheritance in families and genetic factors involved in the severity and triggers for asthma attacks. In 1984 Michael Lebowitz, Robert Barbee, and Belton Burrows looked at 350 families and found that in those where neither parent had asthma, 6% of the children had asthma; when one parent had asthma, 20% were affected; and when both parents had the condition, 60% of their offspring were affected ("Family Concordance of IgE, Atopy, and Disease," Journal of Allergy and Clinical Immunology, vol. 73, no. 2, February 1984).
In their 1995 study of pairs of twins in which at least one twin had asthma, Edward P. Sarafino and Jarrett Goldfedder discovered that genetics and environment both made strong contributions to the development of the illness ("Genetic Factors in the Presence, Severity, and Triggers of Asthma," Archives of Disease in Childhood, vol. 73, no. 2, August 1995). If asthma was directed solely by genes, then 100% of the identical twins, who are exactly the same genetically, would be expected to have asthma (the concordance rate is the rate of agreement, when both members of the pair of twins have the same trait). Instead, the study found that just over half (59%) of twins both had asthma. If asthma was entirely environmentally caused, then genes should make no difference at all—the concordance rate would be the same for identical and fraternal (nonidentical) twins. Sarafino and Goldfedder found that the concordance rate of 59% was more than twice as high in identical twins as in fraternal twins (24%). This research offered clear confirmation that asthma has a significant genetic component.
Asthma is an example of a condition that is polygenic—controlled by more than one gene. Familial studies have demonstrated that asthma does not conform to simple Mendelian patterns of inheritance and that multiple independent segregating genes are required for phenotypic expression (polygenic inheritance). Nevertheless, it has long been known that the complex phenotypes of asthma have a significant genetic contribution. Researchers speculate that several genes combine to increase susceptibility to asthma and that there are also genes that lower susceptibility to developing the condition. Genes also affect asthma severity and the way people with asthma respond to various medications.
Environmental triggers for asthma include allergens such as air pollution, tobacco smoke, dust, and animal dander. Other environmental factors linked to its development are a diet high in salt, a history of lung infections, and the lack of siblings living at home. Researchers speculate that younger children in families with older siblings are less likely to develop asthma because their early exposures to foreign substances (such as dirt and germs) brought into the home by older siblings heighten their immune systems. The enhanced immune response is believed to have a protective effect against asthma and other illnesses.
In "The Genetics of Asthma" (Seminars in Respiratory and Critical Care Medicine, vol. 23, no. 4, 2002), Harvard Medical School researchers Michael Wechsler and Elliot Israel acknowledged some of the difficulties faced by researchers studying a complex disease such as asthma. They describe the following challenges faced by geneticists seeking to pinpoint the genetics of asthma:
Population studies suggest that asthma is a polygenic disease, with many diverse locations of possible asthma genes already identified.
- The definition of asthma can vary from one health care practitioner to another. Some make the diagnosis based on changes in airway reactivity, others on levels of airway function, and still others on clinical symptoms. As a result, phenotyping methods must be examined and compared carefully since the variety of clinical symptoms a patient with asthma may present, such as cough, shortness of breath, wheezing, and chest tightness, are also common to several other conditions such as bronchitis or heart failure, and confusion may result in misdiagnosis.
- While a clinical history of asthma symptoms or phenotypes often suggests a diagnosis of asthma, there is no definitive, specific definition that classifies an individual as having or not having asthma. As a result, some people may be incorrectly labeled or identified, potentially yielding false data or nonreplicable results.
- Several recent epidemiological (the study of the spread of disease in a population) studies suggest that asthma may have many different phenotypic expressions at different ages as assessed by their risk factors and prognosis. For example, children under age six who at various times experience wheezing are labeled as asthmatic. However, most of these children do not continue to have asthma symptoms as they age—they seem to outgrow the condition.
- Asthma differs in terms of severity (mild, moderate, or severe and intermittent or persistent), suggesting different genetic or environmental influences and triggers. There are also several different subgroups of asthma patients, including aspirin-sensitive asthmatics and exercise-induced asthmatics. Each of these variations may have a different biological mechanism that accounts for each individual's phenotype.
The researchers concluded that while a small percentage of cases of asthma may result from a single gene defect or a single environmental factor, asthma is a complex genetic disease that cannot be explained by single-gene models. In most instances it appears to result from the interaction of multiple genetic and environmental factors. Similar to other complex diseases such as diabetes and hypertension (high blood pressure), the complexity of asthma genetics may be characterized by the contribution of different genes and different environments in different populations. Population studies of asthma face challenges comparable to genetic studies of other common complex traits. They are complicated by genetic factors such as incomplete penetrance (transmission of disease genes without the appearance of the disease), genetic heterogeneity (mutations in any one of several genes that may result in similar phenotypes), epistasis (when the effects of multiple genes have a greater effect on phenotype than individual effects of single genes), polygenic inheritance (mutations in multiple genes simultaneously producing the affected phenotype), and gene-environment interactions.
Genetic susceptibility is the concept that the genes an individual inherits affect how likely he or she is to develop a particular condition or disease. When an individual is genetically susceptible to a particular disease, his or her risk of developing the disease is higher. Genetic susceptibility interacts with environmental factors to produce disease, but genes and environment do not necessarily make equal contributions to causation. Genes can cause a slight or a strong susceptibility. When the genetic contribution is weak, the environmental influence must be strong to produce disease, and vice versa.
In most instances a susceptibility gene strongly influences the risk of developing a disease only in response to a specific environmental exposure. If the environmental exposure occurs infrequently, the gene will be of low penetrance, and it may seem that the environmental exposure is the primary cause of the disease, even though the gene is required for developing the disease. For this reason, even when environmental agents are suspected to be a major cause of a particular disease, there is still the possibility that genetic factors also play a major part, particularly genetic mutations with low penetrance. Similarly, a critical mix of nature and nurture is likely to determine individual traits and characteristics. Genetic factors may be considered as the foundation on which environmental agents exert their influence. Based on this premise, it is now widely accepted that while certain environmental factors alone and certain genetic factors alone may explain the origins of some traits and diseases, most of the time the interaction of both genetic and environmental factors will be required for their expression.
Since the 1990s researchers have identified more and more genes that influence an individual's susceptibility to disease. Scientists have already linked specific deoxyribonucleic acid (DNA) variations with increased risk of common diseases and conditions, including cancer, diabetes, hypertension, and Alzheimer's disease (a progressive neurological disease that causes impaired thinking, memory, and behavior). The questions that persist in the genes-versus-environment debate no longer focus on whether a particular trait or disease is caused exclusively by a specific gene. Instead, researchers continue to explore the extent to which genes and environment influence the development of specific traits, especially conditions linked to health and susceptibility to disease.
Examples of the kinds of questions about susceptibility that geneticists and other medical researchers hope to answer include:
- Why so some tobacco smokers live long, healthy lives while others develop lung cancer and die early?
- Why do some people who are repeatedly exposed to human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS), resist contracting the virus?
- Why do common allergens (substances that cause allergies) cause moderate discomfort for some people and life-threatening asthma for others?