A Cell's Journey: Repository Plays Key Role in XP Research

The progress in nucleotide excision repair research could be traced in the journey of cells--from donor, to clinician, to repository, to researcher, and into the literature. The journey began with a sample from a patient with xeroderma pigmentosum (XP), taken by skin biopsy by National Institutes of Health scientists from a young United States man in 1972. The disease provides a good model for understanding the mechanisms behind nucleotide excision repair: Patients with XP have mutations in both copies of one of seven genes, rendering many of the patients' DNA repair mechanisms inoperable. XP patients can't fix damage caused by ultraviolet light and, consequently, are up to 1,000 times more susceptible to skin cancer than is the U.S. population in general. The cells were deposited at the Coriell Institute for Medical Research, in Camden, N.J., founded in 1953 by Lewis Coriell. "At that time, the cell repository was just starting up and we gave our whole collection of cells to them," comments Kenneth H. Kraemer, a research scientist at the National Cancer Institute. Since then, this collection of XP mutant cells, which receives funding from the National Institute of General Medical Sciences, has grown to include samples from 81 individuals. The collection now contains representatives from each of the disease's seven complementation groups (labeled A through G). The XP samples are part of a collection of more than 1,000,000 samples--the largest collection of living cells in the world. The entire collection resides in one room at Coriell, a room crammed with stainless steel tanks. The institute is building an addition so that it can house even more cells. Each tank is divided into six sections containing 51 canisters. Each of those canisters can hold 120 ampules, which are frosted with crystals as a result of a liquid nitrogen bath. The samples revolve on a lazy Susan platform. Although in theory the cells are immortalized, in practice their lives are finite; repeatedly growing the cells can, in time, alter their genetic makeup. "It requires constant effort to keep cell types in stock," Robert Johnson, the institute's director, notes. The institute also tries to keep original samples, while growing others in culture to send out to researchers around the world, for about $75 a vial, plus shipping and handling. (The center insists cells must be received in 24 hours to preserve their integrity.) "We try very hard not to deplete important stock," Johnson notes. Keeping the institute's XP stock can be especially problematic. The disease is rare; some complementation groups appear in one in 250,000 while others appear in one in 1,000,000. "I'm searching at the moment for XPE," Johnson notes while he conducts a tour of the facility. "We're very short on it, and it's important scientifically." Christine M. Beiswanger, who manages the institute's cell culture laboratory, notes that growing any cell repeatedly from a small sample can be difficult. XP cells --like many rare cell types--are especially hard to culture. That makes extracting DNA from the samples difficult, because the process requires a relatively large number of cells, notes Patrick K. Bender, the director of the institute's molecular biology lab. Kraemer notes that XP is probably more understood than some other single-gene disorders, because researchers from all over the world have contributed XP cells, and Coriell sends samples to any licensed research institution after reviewing its research protocol. "There have been other fields with other rare diseases where the researchers get the cells and keep them and try to do everything themselves." James E. Cleaver, professor of dermatology at the University of California at San Francisco, who identified the DNA repair disorder in 1968, calls the collection "invaluable, especially because it contains samples from patients with a wide range of phenotypes. "A lot of the initial genetic identification of the disease--that it occurred in several different forms--were all categorized with cell lines that were laid down here," Johnson notes. Later a group of researchers picked apart many of the repair mechanisms by constructing a cell-free DNA repair system. It is difficult to track the impact of the Coriell cells in the literature, because such records have only been kept since 1988. Since then, 250 papers have acknowledged Coriell for its XP contributions. Countless other papers have doubtless been affected by them.

A Cell's Journey: Repository Plays Key Role in XP Research

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