Response to “Regarding Mole-rats and Cancer”

My coauthors and I thank Welsh and Traum for their interest in our reports of cancer in naked mole-rats (NMRs) and their thoughts regarding potential mechanisms of carcinogenesis in these 2 cases. With these limited cases, it is arduous to determine exact mechanisms of cancer development in this seemingly cancer-resistant species. However, we are delighted that our publications have generated more scientific discussion and inquiry about these unique rodents and their role as animal models for aging and cancer studies. In fact, another paper was recently published documenting 4 additional cases of cancer in a different zoo colony. ⁵

The oxygen levels within the NMR exhibits were tested and are consistent with levels found in ambient air (∼21%; FiO₂ readings: 20.8%–20.9%). Therefore, there is no evidence of long-standing or intermittent hypoxia in these zoo environments. As such, there are no mechanisms to decrease oxygen levels in these NMR exhibits, which are the same as indicated in the standard husbandry practices for NMRs in research laboratories. ¹

Several other parameters for NMR husbandry must be strictly adhered to for successful maintenance, social order, and breeding of NMRs in captivity. Questions have arisen regarding the habitat conditions and husbandry and breeding practices at the zoologic institutions from which these 2 NMRs came, specifically in comparison with research settings. This is particularly interesting as, to date, there have been no official reports of cancer in research NMRs.

Zoologic institutions follow established guidelines based on the natural history and behavior of wild NMRs, to ensure the optimal health and well-being of these zoo colonies. ⁶ Of note, these husbandry standards and practices are virtually identical to those published for NMRs in research settings, with the exception of burrow designs and aesthetics, as the purposes differ: exhibition of animals versus production of animals. ¹ Specific habitat factors include temperature (82°F–87°F), humidity (30%–50%), illumination (minimal, no direct sunlight), and space with interconnecting tubes and specialized “burrow” compartments, including a nursery and latrine. Zoo NMRs maintain a eusocial hierarchy, with 1 breeding queen, several breeding males, and both male and female nonreproductive workers. Recently, new husbandry techniques have been introduced to improve neonatal NMR survival in research laboratories to increase colony productivity. ⁴ The described diets of NMRs in zoo and research settings are similar and aim to maintain healthy gut flora and dentition, cecotrophy behaviors, and adequate enrichment.

One important difference between research NMRs and zoo-housed NMRs is routine and thorough disease surveillance. While research NMRs are monitored for clinical or gross disease, data are limited on the histologic lesions of these colonies. Notably, we found several microscopic diseases in our retrospective study of zoo NMRs that were overtly healthy and carrying out normal behaviors and eusocial lifestyles, including breeding. ² Furthermore, the gastric tumor in case No. 2 from our report was so small as to not be discernable grossly and was detected only microscopically. ³ Thus, this cancer would have gone undiagnosed if complete histologic evaluation had not taken place. Zoo-housed NMR colonies are treated like all other zoo fauna and receive systematic diagnostic workups to determine causes of morbidity and mortality, to optimize care and treatments of future cases, to learn more about health and disease in various species, and to improve conservation efforts of species in their natural environments. Our report of cancer in 2 NMRs does not detract from their profound resistance to carcinogenesis; however, it does highlight the importance of examining the entire animal at the gross and microscopic levels to rule out the presence of neoplastic disease.