Cephalopods in Research

Request for Information

OLAW requested input on proposed guidance for use of cephalopods in research, research training, experimentation, or biological testing or for related purposes between September 8, 2023 and December 22, 2023.  

The proposed text can be found here: NOT-OD-23-176

The comment period is now closed. The final text will be published once comments have been considered.

OLAW Summary of Responses to the NOT-OD-23-176

In response to the Request for Information (RFI) on Proposed Guidance to Assured Institutions on Cephalopod Care and Use, the Office of Laboratory Animal Welfare received 75 comments, many of which included substantive information and detailed recommendations. Comments reflected several positions, with many supporting the proposed guidance in the RFI and others expressing concerns. Several supporting statements viewed the proposed guidance in the RFI as providing protections while maintaining flexibility for institutions and IACUCs. The concerns can be classified in four general categories:

• Insufficient Measures: Some commenters voiced concerns that the proposed measures were insufficient to improve welfare.
• Legal and Procedural Barriers: Other notable concerns included both the lack of sufficient standards for cephalopods in research, and existing U.S regulatory and procedural limitations. The latter included concerns regarding limitations of the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training; and the definition of “animal” in the Public Health Service Policy on Humane Care and Use of Laboratory Animal (PHS Policy).
• Missing Foundational Guidance: The PHS Policy requires that animal care and use programs of Assured institutions be based on the Guide for the Care and Use of Laboratory Animals (Guide). However, there are no standards specific to cephalopods in the current 8th Edition of the Guide, which impedes development of clear guidance.
• Funding: Commenters noted that funding opportunities for basic research in cephalopod biology and welfare to fill knowledge gaps would be welcome. There are currently gaps in knowledge regarding species specific requirements. There are also gaps in the understanding, evaluation, and management of pain and distress in cephalopods, methods of euthanasia, and numerous other aspects of care for research cephalopods.

Some commenters discussed the potential application of international guidelines to cephalopod use in the United States. However, these may not address the needs of U.S. institutions, as guidelines adopted in other countries are employed under distinct regulatory and scientific frameworks. Additionally, cephalopod usage varies globally, and current guidelines reveal significant gaps that necessitate further research to address cephalopod welfare and develop scientifically supported standards of care.

Currently, the PHS Policy is limited to “live, vertebrate animals…” (PHS Policy III.A) and “requires institutions to use the Guide for the Care and Use of Laboratory Animals (Guide) as a basis for developing and implementing an institutional program for activities involving animals.” (IV.A.1) However, the Guide does not address cephalopods in detail, but instead “establishes general principles and ethical considerations that are also applicable to these species.” (Guide p. 2) Without clear standards for the care and use of cephalopods provided in the context of our existing regulatory system, however, institutions would struggle to achieve compliance in their programs, and evaluation of compliance would be difficult to assess and consistently apply. As a result, OLAW would be very limited in how it could determine if something is a noncompliance. More information is needed to develop measures that fully address cephalopod welfare for the variety of species (with varying biological needs) that may be under study. To this end, commenters emphasized that funding is essential for basic research in cephalopod biology and welfare to develop data-driven standards necessary for establishing a regulatory compliance framework.

An August 10, 2026, snapshot analysis reported thirteen NIH-awarded projects using live cephalopods, with eleven of these active. While comprising less than 0.03% of NIH grants, it is critical to address the welfare of these animals in detail and with evidence-based information because of the complexity and range of species-specific welfare needs. In response to the legitimate concerns raised by commenters about the proposed guidance, issuance of final guidance is currently paused pending further development of evidence-based standards, release of the next edition of the Guide and any applicable legislative or policy developments. In the interim, OLAW encourages institutions to take steps to ensure the humane care and use of invertebrates and refer to professional publications for husbandry, minimization of pain and distress, and management best practices. IACUCs have the discretion to oversee studies involving cephalopods as they would vertebrate animals; however, reports to OLAW should not include cephalopods at this time unless specified otherwise in your institution’s approved Animal Welfare Assurance.

Cephalopods in Research

Cephalopods are a class of invertebrate aquatic animals that includes octopuses, nautiluses, squid, and cuttlefish. These animals belong to the phylum Mollusca, which includes several other invertebrate species such as bivalves and snails. Distinguishing features of cephalopods include a head-like structure, arms and/or tentacles, and a hard beak structure. There are over 800 known species of cephalopods worldwide. 

Cephalopod research has been conducted for over 100 years. These studies have provided valuable insight into the science of learning, motion and movement, behavior, and nervous system development. Recent initiatives to formalize standards for cephalopod care and use are helping to ensure continued humane treatment and honor the principles of the 3Rs: Replacement, Reduction, and Refinement.

Quick References

OLAW provides these resources as a courtesy and any questions regarding the content should be addressed to the authors. OLAW is providing them for informational value and not as regulatory guidance. The information in each article does not necessarily represent the views of the NIH.

Please email suggested resources to the Division of Policy and Education at [email protected]. Commercial entities are not eligible for listing.

Useful External Guidelines

The following list provides a limited collection of guidelines for the care and use of cephalopods authored by various institutions and professional associations worldwide. While not considered official guidance for Assured Institutions by OLAW, the information presented in these references may be useful in designing high-quality programs that ensure good animal welfare.

• FELASA Guidelines for the Care and Welfare of Cephalopods in Research
• AAALAC Reference Resources: Cephalopod Guidelines (PDF, 1.06 MB)
• NASA Cephalopod Directive

Databases and Organizations

The following additional links provide the names of databases and professional organizations that promote responsible use of cephalopods in research:

• NORECOPA: Cephalopods in research database
• CephsInAction
• Association for Cephalopod Research "CephRes" (Training materials available under "training resources")

Compliance Unit Standard Procedure (CUSP) Sharing Site

The Compliance Unit Standard Procedure (CUSP) Sharing Site is an online repository where participating institutions can share standard procedures used in animal care protocols, supporting the development of high-quality protocols, while reducing burden for researchers, IACUCs, and IACUC support staff. The goal is to assist institutions to easily build a library of standard procedures to use for multiple purposes, such as variations on commonly used techniques, practical information for non-typical species, and methodology used in wildlife studies.

Laws, Policies, and Guidance

Laws and Policies

Though cephalopods are not covered under the PHS Policy on Humane Care and Use of Laboratory Animals (PHS Policy), institutions are expected to adhere to the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training for humane care and use of all animals in their care. In addition, because cephalopods are not vertebrate animals, they are not currently subject to the requirements for reporting and there is no requirement to submit a Vertebrate Animals Section for cephalopod use in funding applications.

Guidance

Pain Perception, Neurobiology, Cognition, and Learning

OLAW provides these articles as a courtesy and any questions regarding the content should be addressed to the authors. OLAW is providing them for informational value and not as regulatory guidance. The information in each article does not necessarily represent the views of the National Institutes of Health (NIH).

Please email suggested resources to the Division of Policy and Education at [email protected].