Friday, May 28, 2010

A more perfect union: Basic Science meets Public Health

If public health is science painted with broad brush strokes, basic science is pointillism — the art of connecting infinitesimal dots.

Public health engages with populations of people; basic science pores over populations of mosquitoes, cells and enzymes. But in a public health setting, the endgame for these bedfellows is the same—large-scale prevention of disease.

So how does the study of mechanisms in cells and tissues at their most fundamental levels complement the public health mission to protect millions? The answers are myriad, all hinging on translation.

As you’ll read in this case study from the Johns Hopkins Public Health journal, disciplines such as toxicology, biochemistry, molecular and microbiology, epidemiology, and biostatistics can endlessly inform each other, and lead to cross-fertilization, clues, predictions — and ultimately — solutions to the world’s most vexing health problems.

Virus Plus Toxin Equals Cancer

In China’s Jiangsu province, the rates of liver cancer far outpace the global averages, and its victims are far younger than elsewhere. At a population level, Jiangsu is an obvious outlier. “Any time you see a lack of uniformity in disease, it smacks you in the face, and you realize that there must be dramatic exposures to something in the environment,” says chemist and toxicologist John Groopman, PhD, chair of Environmental Health Sciences (EHS).

Thirty years ago, Thomas Kensler, PhD, a toxicologist and professor in EHS, considered the questions posed by the epidemiological research in Jiangsu, and he began to look for answers on a molecular level. Hepatitis B (HBV), which is four times more prevalent in Asia than in developed nations, was part of the explanation.

Could there be a chemical agent, a “DNA damage product,” operating in conjunction with HBV? Kensler and Groopman identified just such an agent, which works with HBV to create mutations in a tumor-suppressor gene known as TP53—the most commonly mutated gene in all human cancers. The agent, aflatoxin, is a product of moldy crops such as peanuts and corn, is ubiquitous in Jiangsu, and can’t be cooked out of food. By itself, it can mutate cells in small measure. But a person who has biomarkers for both risk factors—aflatoxin exposure and HBV—has 60 times more risk of developing liver cancer than someone who has neither biomarker.

The translation of these basic science discoveries is a two-pronged population-wide prevention plan that incorporates vaccinating against HBV at birth, and communications programs that help Jiangsu residents to consume less aflatoxin. Both efforts are now under way.

The toxicologists are also exploring ways to diminish the impact of unavoidable exposure to aflatoxin. With a clear molecular target—the antioxidant signaling pathway Nrf2, which eliminates toxins and protects against mutations to TP53—they’ve conducted clinical trials involving drugs and compounds that include oltipraz, chlorophyllin, sulforaphane and tea made from broccoli sprouts. All compounds were found to significantly reduce DNA damage. “And even a modest reduction in DNA damage,” says Groopman, “can confer quite a large reduction in cancer.”

Story by Christine Grillo
Illustrations by Brad Yeo

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