A Genetic and Environmental Disease
Although we divide diseases into “genetic” and “infectious” categories, many diseases are influenced by a combination of factors. These diseases are harder to classify and treat than diseases that are caused by one determining factor. Many researchers have studied leukemia, but the underlying cause of the disease has not been conclusively demonstrated. Leukemia is not caused by a disease organism and is not infectious. It is a genetic disease, in that it is caused by malfunctioning genes, but it is acquired rather than inherited, with the exception of CML. It is caused by an injury to the genes of bone marrow cells. This injury, which makes the cells function incorrectly, also gives them a competitive advantage over normal cells, allowing them to multiply and replace normal cells.
This genetic damage seems to have a variety of causes. Risk factors may lie in a person's genetic inheritance. People with Down's syndrome and certain other genetic disorders are also more likely to get leukemia (Robien and Ulrich, 2003). In some cases, leukemia seems to run in families. This may be due to an inherited susceptibility to gene abnormalities. In addition, population studies have shown that unlike other cancers, immigrant groups retain the leukemia risk of their countries of origin rather than their new environments, suggesting an important genetic role in the disease (Robien and Ulrich, 2003).
More often, leukemia is caused by a person's exposure to a substance in their environment. Environmental risk factors affecting adults include “exposure to radiation, benzene, pesticides, cigarette smoke, and extremely low-frequency electromagnetic fields” (Robien and Ulrich, 2003). Each of these environmental factors induces genetic mutation, which can lead to leukemia. However, in most cases of leukemia, none of these risk factors are present. Leukemia often develops in people with no family history of the disease or significant exposure to any of the environmental risk factors.
Mel Greaves, a prominent leukemia researcher, has suggested that ALL leukemia develops in two stages: a pre-natal genetic mutation that predisposes a patient to the disease, and a post-natal exposure to one of the risk factors listed above. Several studies have indicated that the factor that triggers leukemia may be an abnormal immune system response to a common infectious disease like the flu. Researchers have correlated infection with the onset of leukemia, particularly ALL (Robien and Ulrich, 2003, Taub and Ge, 2004). According to Jeffrey Taub and Yubin Ge, "Greaves has hypothesized that ALL develops via at least two mutations with the first mutation occurring in utero and the second mutation occurring postnatally as a result of exposure to an infectious agent" (Taub and Ge, 2004). A study in the U.K. found that children who were exposed to fewer infectious diseases, as measured by their degree of social activity, had a greater chance of developing ALL (Gilham, et al, 2005). This is an indirect measure of the children’s exposure levels, but other studies “directly assessing incidence of common infections” also show that children who have contracted some infectious diseases, such as ear infections, have a lower risk for leukemia (Robien and Ulrich, 2003). It may be that an inadequately trained immune system stresses the body and causes the gene abnormality to be expressed.
The Environment of Evolutionary Adaptedness
The human body evolved over millions of years in distinct environmental conditions. Evolutionary biologists refer to this environment as the environment of evolutionary adaptedness (EEA). Although researchers do not always agree about the exact conditions for which our bodies are adapted, they agree that our present environment does not match the EEA. This is particularly true in industrialized nations such as the United States of America, where people have been able to substantially alter their environment to suit their needs. Unfortunately, natural selection has not been able to keep pace with the speed with which people are changing their lifestyles. Many diseases result from the misalignment of the environment we live in and the environment for which our bodies are designed.
An Evolutionary Explanation for Leukemia
In general, cancers like leukemia exist today partially because in the past there was evolutionary pressure both to encourage mutations and to restrain them. Regulatory and surveillance genes found in multicellular organisms have ancestors going back a billion years (Greaves, 2000). The variation caused by mutation has been an evolutionary advantage, because it allows natural selection to operate effectively. Mutations occurring far in the past affect us now because they were advantageous in the past, even if there may be some negative consequences now. Genes that allow extensive proliferation of cells are necessary for cancer to develop, but they are also necessary for embryo development, creation of organs, pregnancy, healing of wounds, inflammation, and tissue renewal (Greaves, 2000). Organisms have also evolved mechanisms to control mutation and proliferation of cells because if they had not, cancer would have reduced their reproductive success (Greaves, 2000). Many stages must occur before a cell will cause cancer. The gene must mutate and remain unrepaired, have mutated in a way that impairs the function of the protein that it codes for, and must provide a reproductive advantage for that particular cell and its descendants. Generally several gene mutations are necessary for this to happen (Greaves, 2000).
Leukemia is a complex, multifaceted disease, resulting from the interactions between people's genes and their environment both in and out of the womb. However, we can draw broad conclusions about why natural selection has not eliminated leukemia, particularly childhood leukemia, from the human population. Randolph Nesse and George Williams categorize “novel environments” as a major cause for the diseases that affect the world today. The increase of childhood leukemia in modern times may be lifestyle-related. In developed countries, families are usually smaller and hygiene has improved. Infants are no longer exposed to infections at as early an age (Greaves, 2000). Our immune systems have evolved to respond to infections shortly after birth, usually through the mother's antibodies during breast-feeding. During earlier periods of urbanization that increased population growth, there may have been selection for infants whose immune systems responded the most quickly and most effectively to infections (Greaves, 2000). The immune systems of children exposed at later ages, without having confronted microbes at an earlier age, may not respond as well and may increase their risk of developing leukemia (Greaves, 2000). The incidence of leukemia is higher among more industrialized nations, and in those nations among people of higher socioeconomic status, because these people are living in an environment that is least like the EEA. People in these privileged positions are exposed to more pesticides and chemicals, and fewer infectious diseases, than people living in less rarified conditions. Leukemia may be the tragic consequence of our "success" as humans at altering the environment we evolved to live in.
Created by Shannon McGlauflin, Jolene Munger, and Rebecca Nelson, 2005.