The Chemical Detective

Sitting on a bookshelf in David Malarkey’s third-floor office is a collection of 1950s-era brochures touting the benefits of wondrous new synthetic chemicals. Malarkey, who works for a federal program charged with determining the toxicity of various substances, picks up one of the booklets and begins reading aloud about a pesticide called chlordane, which was used until the 1980s to kill garden insects. “Effective for long periods of time, safe when applied as directed,” he reads. “Outdoor living will be more comfortable when used to kill these pesky chiggers, mosquitos and flies.”

“I don’t know how safe it was,” Malarkey says with a note of sarcasm. He wrote his Ph.D. thesis on chlordane, one of the most potent carcinogens ever tested in animals, back in the 1990s. These days, Malarkey, V89, runs the pathology group at the National Toxicology Program, or NTP, which is part of the National Institute of Environmental Health Sciences (NIEHS).

Working out of the institute’s sprawling brick headquarters in the Research Triangle Park of North Carolina, his pathology group assesses the safety of the chemicals in our foods, medicines, households and workplaces. On Malarkey’s desk is a two-foot-high stack of toxicology reports and a large microscope that he uses to scan slides for cellular features of cancer or toxic side effects.

“People often say that there are 80,000 chemicals in our products and our environment, but the real number may be more like 800,000,” Malarkey says. Then there are the hundreds of thousands of new chemicals constantly being made and introduced into our lives through cosmetics, foods, household cleaners, clothing, pharmaceuticals and lawn products. “We need to show that these agents are safe, or at least not hazardous,” he says.

Malarkey grew up in the suburbs of Connecticut. His father, a science teacher and avid birdwatcher, released plenty of orphaned and injured birds back into the neighborhood as a wildlife rehabilitator, but Malarkey longed to raise farm animals and be a vet. However, once in veterinary school, he gave up the idea of treating or raising farm animals after being kicked by a cow. The incident solidified his interest in studying the causes and effects of diseases, a science he had learned to love from an undergraduate professor of pathology.

In 1989, Malarkey began a two-year residency at Angell Animal Medical Center in Boston, and then worked as an anatomic pathology instructor at North Carolina State University College of Veterinary Medicine (NCSU) until 1993. Along the way, he became increasingly interested in the molecular underpinnings of cancer.

For four years, he worked on his Ph.D. at NCSU, conducting his research at the NIEHS. After earning his degree in molecular pathology, he was appointed an assistant professor of pathology at NCSU. He accepted a position at the NTP in 2002 and three years later, took charge of the NTP’s Pathology Group. He now also serves as the president of the American College of Veterinary Pathologists.

The NTP was established in 1978 after tragedies like Love Canal—in which more than 900 families were exposed to hazardous chemicals when schools and homes were built on top of a toxic waste dump in Niagara Falls, New York—heightened public awareness about the health effects of toxic chemicals.

Finding the Culprit

Determining whether a chemical poses a threat to humans is slow and painstaking work. To date, the NTP has examined more than 2,800 agents and identified a number of serious problems—about half of the 600 agents tested for cancer-causing properties thus far have shown evidence of causing cancer in animals.

The substances that the NTP decides to study usually have been flagged because there is some evidence that they could pose a threat to public health, such as a biochemical profile that matches known toxins or carcinogens, or work done by others that indicates a problem—for instance, Erin Brockovich’s well-known investigations into hexavalent chromium, the chemical that poisoned residents of Hinkley, California.

One of the worst offenders identified by NTP researchers is phenolphthalein, a chemical that served as the main ingredient in many over-the-counter laxatives for most of the 20th century. The NTP’s animal studies found that phenolphthalein causes thymic lymphoma and connective tissue tumors, as well as abnormal growths on the ovaries, adrenal glands and kidneys. Pharmaceutical companies quickly replaced phenolphthalein with senna, a natural chemical derived from the leaves of the senna plant.

Other times, however, the NTP’s work winds up exonerating a chemical. During the 1980s and 1990s, the town of Toms River, New Jersey, experienced an abnormally high number of childhood cancer cases. Around the same time, hundreds of chemicals, including a new entity called Styrene-Acrylonitrile Trimer (SAN Trimer), appeared in the town’s drinking water. SAN Trimer was widely believed to be the cause of the increase in the cancer rate, but when the NTP tested the drug on rodents, it found no evidence that it caused cancer. (The study did find that the chemical had other detrimental effects, including peripheral nerve damage, for the exposed rats.)

When it came time to deliver the news to residents of Toms River that SAN Trimer was not the culprit, the task fell to the Environmental Protection Agency, but members of Malarkey’s staff shared the NTP findings at a public meeting. Malarkey says it was important to explain the negative findings face-to-face because it was such an emotionally charged issue.

“Mostly, we took time to listen to their concerns,” says Susan Elmore, a veterinary pathologist who spoke at the meeting. “They wanted answers. They wanted to say that it was this chemical that gave their children cancer. But there were many other things in the water. We can’t possibly test every one or every possible combination.”

The NTP typically relies on animal testing to evaluate chemicals. In studies that last for two weeks, three months or two years, the animals are given treatments of a chemical in varying doses, with some animals getting none at all. Malarkey says the NTP would like to decrease its dependence on animals and develop alternative testing methods that are equally effective and less expensive. “Right now we don’t have a better way to determine the safety of the chemicals in our environment, but we are leading some international efforts to make this happen,” he says. “Personally, I would rather get rid of animal testing altogether, and one day that may be possible.”

Genetics offers a promising alternative. It’s still early, but Malarkey and his NTP colleagues are working to identify the patterns of gene expression seen in blood and tissues from people and animals that have developed cancer. The researchers have found that they can link gene changes with specific changes in cells, such as death or inflammation, and they hope to someday use these patterns to predict which chemicals are likely to cause cancer simply by exposing cell lines, instead of animals, to these agents in the lab.

For now, Malarkey has plenty to keep him busy. “The one thing I do worry about is the pollutants being put into the environment that our kids will have to clean up. It is tough because as industry grows and keeps moving forward, it seems almost unavoidable that chemicals will become a greater part of us. We just have to keep checking and avoiding the questionable ones.”

Marla Vacek Broadfoot is a freelance science writer in Wendell, North Carolina.