The idea that traits are either genetic or environmental is rapidly outliving any usefulness it might once have possessed; these days, scientists are pondering how much each is involved and if they interact.

Recent studies of tuberculosis and malaria are cases in point. In the Dec. 19, 2005 issue of the Journal of Experimental Medicine, researchers reported on a genetic contribution to tuberculosis susceptibility. The report comes about a month after one in the open access journal PLoS Medicine identifying the overall genetic contribution to malaria susceptibility.

Infection with Myobacterium tuberculosum by no means equals disease - only a fraction of people who catch the bacterium also will develop clinical symptoms of tuberculosis.

A weak immune system is one way to progress from latent to active disease, and tuberculosis is feared as an opportunistic disease that often spells doom for HIV-infected patients. Indeed, it is HIV that has made tuberculosis, which was once practically eradicated in developed countries, a problem on the rise.

In the Journal of Experimental Medicine paper, researchers from the University of Texas Health Center at Tyler, Chungnam National University in South Korea, the Dana-Farber Cancer Institute in Boston, and the Mexican Institute of Respiratory Diseases and the Mexican National Institute of Medicine and Nutrition "Salvador Zubiran," both in Mexico's Federal District, reported on a genetic mutation in the promoter for monocyte chemoattractant protein-1 or MCP-1. Its abundance contributes to the development of tuberculosis in those infected with Myobacterium tuberculosum.

MCP-1 is an attractant for cells that help contain M. tuberculosis and is thus thought to help orchestrate the initial response to infection. But MCP-1 follows the "too-much-of-a-good-thing" principle: High levels of the protein inhibit the expression of the cytokine interleukin-12, which helps activate antibacterial effector cells.

The researchers studied single nucleotide polymorphisms in MCP-1, as well as several other tuberculosis response genes, in tuberculosis patients and healthy controls from Mexico. They found that people with one variant of the MCP-1 promoter had an increased risk of developing tuberculosis; carriers of two copies of guanine in position 2518 of the MCP-1 promoter had more than five times the risk of developing tuberculosis than those who had two copies of adenine, while heterozygotes (one guanine, one adenosine) still showed a more than double risk. Monocytes from patients with two guanines produced high levels of MCP-1 and, as a consequence, low levels of interleukin-12 in response to tuberculosis bacterium.

That there are genetic contributions to malaria risk is widely known; indeed, those genetic contributions are literally a textbook case for Mendelian genetics. One mutated copy of the hemoglobin beta gene is a good thing for those who live in areas with malaria risk because it protects them against malaria, but two copies lead to sickle-cell anemia. Hemoglobin beta is the family matriarch of a number of gene variants that have been identified over the years that contribute to malaria risk or protection.

Now, in the Nov. 8, 2005, issue of PLoS Medicine, scientists from the University of Edinburgh, the University of Cambridge and John Radcliffe Hospital, all located in the UK, and the Centre for Geographic Medicine Research in Kilifi, Kenya, have used statistical methods to tease out the relative contributions of genetic and environmental factors to malaria susceptibility. The authors hope that "putting genetic and environmental factors into perspective will inform the design and interpretation of intervention studies aimed at reducing the burden of malarial disease and will help to rationalize research priorities."

The scientists conducted two separate studies: one keeping track of relatively mild cases of malaria in approximately 650 children living in about 80 different households, the second recording severe malaria episodes that resulted in hospitalization in a different group of almost 3,000 children. The scientists took advantage of the East African family structure for their study of mild malaria - a household typically is comprised of a group of three to six houses, each occupied by one woman and her children, and husbands who were full- or half-siblings and who sometimes had more than one wife. Thus each household consisted of several distinct full-sibling, half-sibling and first cousin groups of children, which allowed the researchers to explore household factors (which should affect all children equally) from genetic factors (which vary least between full siblings, more between half siblings, and most between cousins).

The analysis indicated that genetic differences accounted for about 25 percent of malaria risk variability, while household factors accounted for around 30 percent of variability. While known behaviors such as use of insecticides explained some of the between-household risk variability, most of that variability was due to unidentified causes. Bed nets, which are a major malarial risk-prevention strategy, were found to have no effect.

The researchers concluded that "the average risk of malaria in children living in our study area is in large part due to factors that are predetermined, both at the genetic and nongenetic level."

They also believe that "determining how specific genes control the protective response may, ultimately, lead to a better understanding of the mechanisms of pathogenesis and host resistance," but for the short term, "tackling household-related factors would seem to be a more tractable option for disease control."