It took an ogre to make most of us aware of the hazards of cadmium. The soft, silvery white metal—the “cad” in ni-cad batteries—has long been a staple commodity of industry. And it’s spewed regularly into the atmosphere by coal-burning power plants.
But it wasn’t until earlier this year, when high levels of cadmium were discovered in the paint on “Shrek” drinking glasses offered at McDonald’s and in the children’s jewelry sold at big-box and shopping-mall retailers, that the public became alarmed. Regulators and legislators responded by promising to ramp up efforts to restrict cadmium’s use and promote further study of its health effects.
By then, MU’s Jane McElroy had been on the case for nearly a decade, investigating cadmium’s very real potential for increasing the risks of cancer.
The adventurous environmental health researcher in MU’s School of Medicine has a penchant for taking on personal and professional challenges.
McElroy’s office is lined with photos she has taken during her continent-hopping expeditions to Thailand, Chile, Australia and Spain, to name just a few of the places she has explored. She has for years been an Outward Bound instructor, a job she relinquished only recently. When she’s not on the road, McElroy helps build houses for Habitat for Humanity.
“Limitations are what you put on yourself, not what others put on you,” McElroy says. And that’s a succinct way to sum up how she approaches both her life and her work.
Recently returned from kayaking through the ice floes off the Greenland coast, McElroy is launching a new study to determine whether exposure to cadmium might be a risk factor for developing endometrial cancer, a malignancy attacking the lining of the uterus.
In research conducted at the University of Wisconsin, McElroy helped establish a link between cadmium exposure and the risk of breast cancer. She’s expecting to find a similar relationship between endometrial cancer and the toxic metal.
“We would be very surprised if we didn’t see an increased risk,” she says.
Like other heavy metals, such as lead and mercury, cadmium has no beneficial role in human biology. Like those other metals, it can be harmful in even very small amounts. It’s also next to impossible to avoid.
“It’s everywhere. You really can’t point to one source,” McElroy says. “Everybody is exposed to it and everyone has it in their body.”
Until the industrial age, the main sources of cadmium in the environment were natural events such as forest fires and volcanoes, which released it into the atmosphere.
Today cadmium also enters the environment as a by-product of zinc mining and smelting. Most recently, human exposure has come from the manufacture and disposal of those rechargeable necessities of our electronic civilization, nickel-cadmium batteries.
While much of the cadmium in the environment is spread through the air, that’s not the principal way the element makes its way into our bodies. Most exposure comes indirectly. The metal lands on farm fields and on the ocean waters. From there, it is taken up by the food crops and crustaceans we eat.
For example, wheat grains archived over the past century have shown an exponential increase in the cadmium they contain. Another significant source of cadmium exposure is tobacco smoke. Smokers show a two-fold increase in their cadmium levels, and it may contribute to their risk of developing lung cancer.
The recent alarms over cadmium in children’s jewelry came after manufacturers apparently substituted the metal for lead.
When lead was discovered in jewelry and painted toys several years ago, Congress passed the Consumer Product Safety Improvement Act to tighten restrictions. Cadmium is also commonly used as a pigment in yellow paint, which accounts for its appearance on the Shrek glasses.
Cadmium has recognized toxic effects. Acute symptoms such as vomiting and diarrhea can develop when food or water contaminated with large amounts of the metal irritate the stomach. When exposure is long-term, cadmium can accumulate in the kidneys and cause damage.
There are other risks as well. Breathing in high levels of cadmium on the job can cause lung disease and even death. Lung cancer has been linked to occupational exposure, and the U.S. Department of Health and Human Services lists cadmium as a known human carcinogen.
But what we know about cadmium’s health effects is far outweighed by the gaps in our knowledge. Only in the 1970s did scientists begin to study its impact on human health in earnest, McElroy says. Much remains to be done, she adds, particularly in defining its role as a cancer agent.
McElroy has been involved in that effort since the early 2000s, just after receiving her doctorate at the University of Wisconsin-Madison. But before then, her career and personal life were not following a straight line into environmental research.
McElroy was born in Joliet, Ill., but she didn’t stay there long. Her family moved often as she was growing up. She ended up attending 12 schools before starting college at the University of Illinois, Urbana-Champaign. “I was always the new kid on the block,” she says. That experience taught her early lessons in self-reliance.
Going from school to school she was alternately identified as academically gifted or challenged. “Other peoples’ perceptions of you can be wrong,” she realized. “I can’t be both a genius and a moron in the span of three years, and I was labeled that way. Therefore, I did whatever I wanted. What’s stopping you from doing anything? Your own self-limitations,” she says.
McElroy served in the U.S. Peace Corps, teaching math and science in a remote region of Nepal from 1988 to 1991. There she witnessed the rise of the democracy movement that eventually forced the nation’s king to accept constitutional reforms and a multiparty parliament. “It was a very interesting time,” she says.
From Nepal, McElroy ventured to Tokyo to study martial arts, landing there without a job, without command of the Japanese language and without knowing anyone in the country. She spent six years there learning and teaching aikido, a form of martial art, before returning stateside to enroll at the University of Wisconsin.
McElroy chose environmental studies, she says, because she likes being around “cool people. People in environmental studies are cool.”
McElroy entered the graduate program “with a unique blend of skill and experience,” says her mentor and research colleague, Patrick Remington, associate dean for public health at Wisconsin.
“I saw her develop into an outstanding researcher and teacher, motivated by her lifelong interest in environmental health and justice,” Remington says. “She willingly assumed many challenging projects while at the University of Wisconsin that involved learning new skills.”
Remington says McElroy published numerous papers in peer-reviewed journals, presented abstracts at national conferences, and received numerous awards recognizing the quality of her work.
McElroy’s research in Wisconsin included studies that examined the marketing, sales and distribution, and environmental spread of atrazine, a common herbicide used in corn-growing states. Her doctoral dissertation looked at whether the presence of atrazine in drinking water might be responsible for increasing the risk of breast cancer.
She didn’t turn up a relationship there, but she was quickly on to another potential breast cancer risk: cadmium.
Previous research had found higher levels of cadmium in the breast tissue of women with tumors than in women with benign conditions. But there was little evidence outside the laboratory to make the connection between cadmium and breast cancer.
McElroy and her colleagues took advantage of data already being gathered on nearly 15,000 subjects for the ongoing Wisconsin Women’s Health Study in order to find 246 women diagnosed with breast cancer and 254 age-matched control subjects. The women were asked to mail in urine samples, the best test for lifetime exposure to cadmium.
McElroy found that women who had the highest exposure to cadmium were twice as likely to have breast cancer as women with the lowest levels. The Journal of the National Cancer Institute published her findings in 2006.
Recently, another group of researchers found a similar connection between cadmium exposure and breast cancer risk. They looked at the women’s diet, a more indirect measure of exposure. But by then, McElroy had already moved on to the next aspect of her cadmium research.
“It’s important to replicate results, but how can we advance in the field, what’s the next piece that we can add to it?” she asks.
While it hasn’t been proven, McElroy and other researchers think that cadmium may act like estrogen. That may account for the metal’s association with breast cancer; about two-thirds of all breast cancers are fueled by women’s lifetime exposure to the female hormone.
But factors contributing to breast cancer risks are complicated. Not all breast cancers are caused by estrogen. Genetics play a role. And many women who develop the cancer have no known risks at all. “Apparently, we can’t figure it out,” McElroy says.
That is why McElroy was drawn to endometrial cancer as her next subject. “The sweet thing about endometrial cancer is that it is hormone-dependent,” she says. “It may be more straight-forward to study than breast cancer.”
Pull Quote: ‘Women who had the highest exposure to cadmium were twice as likely to have breast cancer...’
Using a four-year, $709,000 grant from the American Cancer Society, McElroy will recruit 750 endometrial cancer patients through cancer registries in Missouri, Iowa and Arkansas and match them to an equal number of controls. All the subjects will be interviewed by phone. As with the breast cancer study, subjects will mail in urine samples. This time they will also be asked to spit a saliva sample into a cup.
A key part of the study takes it beyond simply determining the relative risk of endometrial cancer. That’s why the researchers need the women’s saliva.
Previous research by McElroy and others have found that a particular protein in the body called metallothionein sequesters cadmium and may keep it from harming vital organs. But there are three forms of this protein and they are distributed differently among racial groups.
McElroy will use DNA extracted from saliva to see whether cancer risk is related to the kind of metallothionein the women produce. “From my viewpoint, that is really the big piece we can add to the puzzle,” she says.
McElroy will be working with MU researchers Jerry Taylor, professor of animal sciences and genomics at the Animal Science Research Center, and Elizabeth Bryda, an associate professor with the Research Animal Diagnostic Laboratory, to type the metallothionein in the saliva. She’s also relying on the trace element analysis laboratory stationed at the MU Research Reactor to use mass spectrometry to measure cadmium levels in the urine.
“I come up with ways to make the measurements and Jane drives the fundamental epidemiological questions,” says David Robertson, a chemist and associate director of the research reactor.
“It’s a bit of a challenge to measure. It’s not something to send to any analytical lab. They’d give you a number, but it would be wrong,” Robertson says.
That’s because normally there’s just one part per billion or less of cadmium in urine. Missouri has one of the few labs able to get an accurate reading. “We can measure it at the parts per trillion level,” says Robertson.
McElroy expects the study to take several years. But that hasn’t stopped her from developing plenty of ideas for other projects. She approaches her research with the same fierce confidence with which she has lived the rest of her life. Even for successful scientists like McElroy, such self-assurance is not as common as one might think it to be.
McElroy says colleagues who conduct epidemiological studies can be unnecessarily self-critical—and critical of each other. “We know there are limitations to our work,” she says.
And unlike basic sciences that are often little understood by those outside the field, “everybody knows about epidemiology. That makes it very difficult to get studies funded,” McElroy says. “It’s just a matter of who sees the proposal. In the funding world it’s very capricious.”
McElroy says she has even had grant reviewers tell her “pretty bluntly that I didn’t know what I was talking about.”
She knew better. In one such case, a critical reviewer had put a decimal point in the wrong place.
“I have a couple of unfunded proposals that are brilliant ideas—just nobody agrees with me, yet.” McElroy won’t be deterred. She plans to submit them again.