The newly released Guidance on Significant Changes to Animal Activities1 is intended to expedite aspects of research with laboratory animals. For some situations, however, the intent of the change may not be as obvious as anticipated. For example, the new guidance states that a request for an increase in the previously approved number of animals “may be handled administratively, according to an existing IACUC-reviewed and approved policy without additional consultation or notification.” Yet, when the details become known, what was originally thought to be a clear statement may not be clear, as is illustrated by a question that arose at Great Eastern University.

Dr. Jack Schwartz, a prominent obesity expert, conducted a study using C57Bl/6 mice in which he found that suppressed expression of the gene nol by small interfering RNA resulted in a statistically significant increase in high fat diet–induced obesity. The mice also had an unanticipated significant increase in the incidence of spontaneous mammary adenocarcinomas. Schwartz hypothesized that nol might be functioning as a tumor suppressor gene, and therefore, blocking its activity resulted in a greater cancer incidence. He submitted a protocol modification request to add 50 BALB/c mice to his study to determine if the unexpected cancer finding was unique to the C57BL/6 background or if the results could be reproduced in BALB/c mice. Because the IACUC had a policy in place to allow administrative approval of a request for additional animals, the IACUC administrator approved his request, reasoning that there were no new procedures being requested and that BALB/c and C57Bl/6 mice were both of the genus Mus.

One month later, Schwartz submitted another protocol modification request, this time for the addition of 50 C57BL/6 mice in which a signaling gene in the nol pathway was knocked out. There were no other changes to the experiment. This time, the IACUC administrator wondered if the requested modification was in the spirit of the new regulatory guidance, which appears to have been developed to address a need for additional animals to complete an IACUC-approved experiment. She thought that studying the knocked-out signaling gene was a different experiment than the original one, which was specifically focused on the gene nol. She believed that the new request for 50 more mice should be reviewed by the IACUC for its “societal value,” its potential to advance knowledge and its harm:benefit analysis. In her opinion, the proposed use of the additional animals constituted a different experiment even though no new procedures were being proposed.

Was the IACUC administrator right in approving the request for the BALB/c mice, or does a change in genetic background warrant IACUC review? Did she make the right decision to have the request for the C57BL/6 knockout mice reviewed by the IACUC? Did the administrator overstep her authority?

Response to Protocol Review Scenario: Consequences of flawed IACUC policies

Response to Protocol Review Scenario: Administrator actions appropriate

Response to Protocol Review Scenario: One wrong, one right

Response to Protocol Review Scenario: A word from OLAW