Feedback Sought on Cephalopod Care and Use

Cephalopods are aquatic invertebrate animals that include octopuses, squid, cuttlefish, and nautiluses. Earlier this month, we released a Request for Information (NOT-OD-23-176) seeking public input on the humane care and use of laboratory cephalopods at Assured institutions.   The proposed guidance acknowledges the evidence suggesting these animals would benefit from oversight, but also that there are not yet specific care and use standards to allow them to be regulated under the Public Health Service Policy for the Humane Care and Use of Laboratory Animals (PHS Policy). Instead, the U.S. Government Principles provide a more general and flexible framework until the care and welfare needs of these animals are better characterized.

The Request for Information seeks feedback on the following specific proposed requirements:

• Review of cephalopod activities by Institutional Animal Care and Use Committees or other oversight bodies,
• Semiannual evaluations of cephalopod programs and facilities,
• Use of personnel with qualifications and training relevant to the species being used, as determined by the IACUC or other oversight body, in order to provide appropriate husbandry and veterinary care
• Adherence to cephalopod recommendations of the most current version of the AVMA Guidelines for the Euthanasia of Animals (unless there is scientific justification approved by the IACUC or other oversight body)
• Encouraging the development of institutional policies and standard operating procedures for cephalopod care and use
• Encouraging the sharing of care and use information at conferences and in journal publications

Recent scientific investigations are improving our understanding of invertebrate perception in some species. While there is less information on pain perception in the most used invertebrate models, such as Drosophila (fruit flies) and C. elegans (a kind of roundworm), information is accumulating about cephalopods.

As our guide notice states, a growing body of evidence demonstrates that cephalopods possess many of the requisite biological mechanisms for the perception of pain, such as nociceptors and a centralized nervous system. Cephalopods exhibit adaptive learning, alter their behavior in response to noxious stimuli, and exhibit mammalian-like responses to anesthetics. However, although scientific understanding of cephalopod perception is growing, there are still aspects that are not clear. Species-specific standards for husbandry and housing, and professional standards for veterinary care are still being developed by the veterinary and research communities and require additional scientific study and validation. The relatively small percentage of NIH-funded research using cephalopods is another limitation to comprehensively understand care and use issues.

The Health Research Extension Act of 1985 (HREA) provides the statutory mandate for the PHS Policy, both of which Assured institutions must follow. While the HREA does not define animal, the PHS Policy defines it as “any live vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes.” The Policy defines covered animals and broadly outlines compliance requirements, but it incorporates other documents by reference to provide more specific guidance and standards of care. These documents include the Guide for the Care and Use of Laboratory Animals (Guide), the Animal Welfare Act and its regulations, and the AVMA Guidelines for the Euthanasia of Animals. Currently, only the AVMA Guidelines for the Euthanasia of Animals provide guidance regarding cephalopods.

Because of the lack of scientific understanding and species-specific standards of care, applying the PHS policy to cephalopods is currently challenging.

However, the U.S. Government Principles II, III, IV, and IX outline practices that can be applied to this class of animals despite the current gaps in knowledge, and the other Government Principles can be applied to the extent possible based on applicability and current knowledge. These principles allow more flexibility for institutions, especially in situations where standardized care and use guidance is not well established.

Several selected cephalopod research resources are also available on the NIH Office of Laboratory Animal Welfare site, which will be regularly updated. These resources include the FELASA Guidelines for the Care and Welfare of Cephalopods in Research, AAALAC International’s Cephalopod Guidelines, NASA’s Cephalopod Directive, and selected journal articles. It also includes information on the Compliance Unit Standard Procedure Sharing Site, a Federal Demonstration Partnership project funded in part by the NIH Office of Extramural Research. The site is an online repository where participating institutions can share standard procedures used in animal care protocols, including procedures for care and use of non-typical species.

A focus on proper welfare of cephalopods is also important for rigorous and reproducible NIH-supported research. Back in February, we discussed a guide notice encouraging recipients to include the ARRIVE Essential 10 in all NIH-supported publications describing research in vertebrate animal and cephalopod research. Such information allows the research community and other readers of the journal articles to confidently assess the reliability of the findings presented.

We appreciate your feedback on this request. We will thoughtfully consider all responses received as we develop further resources ensuring the proper humane care and use of cephalopods in NIH funded research. Responses must be submitted electronically by December 22, 2023.