Toenails stashed in Harvard basement could hold clues about cancer

Deep in the basement of Harvard University’s T.H. Chan School of Public Health sit more than a hundred vault-like freezers. Inside them: Toenails.

A whole lot of toenails.

Toenails that may hold the key to a better understanding of ovarian cancer.

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Harvard’s basement biorepository contains 3.5 million samples of blood, plasma, and urine from a nearly four-decade old research project known as the Nurses’ Health Study.

But it’s the toenail clippings from more than 100,000 people — and a similar number of snips of hair from cut-off ponytails — that hold special promise for scientists.

A blood sample only reflects what’s going on in your body in the very moment the blood is drawn. But hair and toenails harbor hormones and trace elements like arsenic and selenium, so scientists can analyze them to get an average of the levels in your body over several months.

That makes the envelopes full of clippings a gold mine for researchers, who have used the samples in at least 400 research projects studying 40 diseases.

Shelley Tworoger, a Harvard epidemiologist who runs the biorepository in collaboration with Brigham and Women’s Hospital, is examining how stress levels coincide with tumor progression in patients with ovarian cancer.

And Dr. Meir Stampfer, also of the Harvard public health school, has used the toenails to study risk factors for cardiac disease. Stampfer compared the mercury levels in toenails from people who went on to have heart attacks to the mercury levels in people who didn’t. He ended up concluding that mercury levels don’t play a role in cardiac problems.

Donor hair samples are stored in binders at the BWH/Harvard Cohorts Biorepository in Boston, Mass.
Alissa Ambrose/STATResearchers will use hair samples, stored in binders at the BWH/Harvard Cohorts Biorepository, to investigate a host of diseases.

Because your toenails grow at different speeds, each one represents a different period in time. A clipping from your little toe captures substances that have been in your body for roughly a month. A clipping from your big toe gives a snapshot of a year’s worth of exposure.

“When you take the edge of the nail of all five toes, you have a measure that stretches over the past year,” Tworoger said.

But toenails also have their limitations.

“With blood, you can draw 40 milliliters at one time, but with toenails, people can only clip back so far,” Tworoger said. The toenails are also tricky to work with — to use them, all five clippings have to be ground up into dust and mixed together to get measurements that average out over a year.

And of course, researchers have to be careful to note any potential contaminants. While hair dye doesn’t impact the snipped-ponytail samples, the researchers have to quiz toenail donors about everything from pedicures to fungal creams to know what they’re looking at with the samples.

When they send in their toenails, hair, blood, and urine, nurses also provide information about stressful events, whether positive or negative, in their lives. They also answer scores of other questions to help researchers correlate the biological analysis of the samples with the donor’s real-life medical and personal experiences.

A donor hair sample at the BWH/Harvard Cohorts Biorepository in Boston, Mass.
Alissa Ambrose/STATA hair sample could provide insight into diseases not found in blood or types of other biosamples.

Early on, researchers didn’t limit the collection to nurses. Marge Dwyer, who lives in a suburb of Boston, recalls a doctor coming into her room after she’d given birth to her first son, back in 1981, to ask for toenail donations.

“The toenail sample request seemed pretty odd,” she said.  But she said she knew it was important for people to participate in research. “Besides,” she said, “it’s no big deal to donate a toenail.”

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