Illustrations by Brad Yeo

A More Perfect Union
Basic Science Meets Public Health

Story by Christine Grillo   

Food Can Fix You

The vitamin D story may have its origins on a Kansas farm, where a young boy helped his father raise pigs. Elmer Verner McCollum and his brother were given the runts of the litter and told that they could feed them as they chose, and keep whatever money the pigs would bring. The boys fed the runts milk, the runts became healthy, and the brothers made a profit.

Years later, as a biochemist, E.V. McCollum used an elegant methodology to answer questions about the basic science of nutrition. With methodical precision, he perfected what is now referred to as molecular nutrition, using lab rats on restricted diets to isolate properties found in foods.

As head of the Department of Chemical Hygiene at the Johns Hopkins School of Hygiene and Public Health, he collaborated with pediatricians and pathologists who wanted to study rickets in a laboratory setting. McCollum fed his rats cod liver oil, used for centuries in Europe to treat the bone disease. Their investigations led to the discovery of vitamin D, the fourth vitamin to be discovered.

But McCollum’s work extended beyond the laboratory. Dedicated to the dissemination of knowledge about nutrition and “protective foods,” he advocated tirelessly for putting milk and leafy vegetables on dinner tables. Over time, McCollum’s discovery was translated into a population-wide prevention program in the U.S.—the fortification of milk and bread with vitamin D. As a result, rickets was eradicated in this country.

McCollum’s department became part of what is now Biochemistry and Molecular Biology (BMB). Pierre Coulombe, PhD, the newly appointed E.V. McCollum Professor and BMB Chair, believes that McCollum’s work represents the mission of all basic scientists working in public health: “If you identify the chemical principle, if you can find the purified substance, that becomes the basis for a potential mass intervention.”

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.”