The Lobund-Wistar rat: a prostate-cancer model from the germfree colony

1970s — today

The rat that gets the disease men get: Lobund's second gift to medicine came out of the colony itself. Morris Pollard, who directed the laboratory after Reyniers and worked with its germfree animals for more than forty years, was monitoring a small colony of germfree Wistar rats when, as he wrote in The Prostate in 1998, he observed tumors in the pelvic region among aged rats of the thirty-sixth and later the fifty-seventh generation — prostatic adenocarcinomas that had metastasized to the lungs. The fifty-seventh generation was conventionalized and propagated as a named strain, the Lobund-Wistar (L-W) rat. Its documented character made it a model the National Cancer Institute adopted: in Pollard's 1998 account, large prostate-seminal-vesicle tumors developed spontaneously in 66 of 244 conventional L-W rats — twenty-seven percent — at an average of twenty-six months; the tumors arise in two stages, an early testosterone-dependent stage and a late hormone-refractory stage, as human prostate cancer does; and a transplantable, metastasizing cell line, PA-III, was derived from a spontaneous tumor in an aged germfree L-W rat.

The model went to work: in Cancer Research in 1991 Pollard, Luckert and Sporn reported for the first time that the synthetic retinoid N-(4-hydroxyphenyl)retinamide prevented both primary and metastatic prostate tumors in the induced L-W model, and the dietary studies followed — the university's magazine reporting that where thirty percent of the rats spontaneously developed the cancer by age two, only three percent of those fed a soy-protein diet did, a finding carried here as the magazine reports it. The university's animal facility states the standing plainly today: the National Cancer Institute's approved model for prostate cancer, the LOBUND-Wistar rat, was developed at Notre Dame and continues to be maintained at the Freimann Life Science Center. Pollard, who published more than three hundred journal articles in the university magazine's count, ran what it called the longest-running medical research program at Notre Dame.

Sources:

1. Morris Pollard, "The Lobund-Wistar Rat Model of Prostate Cancer in Man," The Prostate 37 (1998): 1–4 — the observation of metastasized prostatic adenocarcinomas in the thirty-sixth and fifty-seventh generations of the germfree Wistar colony; the conventionalized strain designated Lobund-Wistar; spontaneous tumors in 66 of 244 rats at an average of twenty-six months; the PA-III line derived from a spontaneous tumor in an aged germfree rat.
2. M. Pollard, P. H. Luckert and M. B. Sporn, "Prevention of Primary Prostate Cancer in Lobund-Wistar Rats by N-(4-Hydroxyphenyl)retinamide," Cancer Research 51 (1991): 3610–3611 — the first report that the retinoid prevented primary and metastatic tumors in the model.
3. M. Pollard and M. A. Suckow, "Hormone-Refractory Prostate Cancer in the Lobund-Wistar Rat," Experimental Biology and Medicine 230 (2005): 520–526 — the model's two-stage, hormone-dependent to hormone-refractory course.
4. Notre Dame Magazine, "Ratting on Prostate Cancer" — Pollard's forty years with the germfree animals and more than three hundred journal articles; the soy-diet finding (thirty percent against three percent) as the magazine reports it; the laboratory directorship and the longest-running medical research program at Notre Dame.
5. Freimann Life Science Center, University of Notre Dame, about page — "The National Cancer Institute's approved model for prostate cancer, the LOBUND-Wistar rat, was developed at Notre Dame and continues to be maintained at FLSC."