Existing Checks and Balances Are Failing

NIH is the largest funder of biomedical research in the world, and the U.S. has been estimated to be among the world’s largest users of animals in experimentation,¹ but the lack of transparent accounting of animals used makes accurate numbers impossible to determine. Despite the existence of laws and committees expected to protect animals in laboratories, no experiments—no matter how harmful—are prohibited. Outdated and incomplete ethical frameworks, insufficient care and welfare standards, lax enforcement, self-serving committees, and the exclusion of 95% to 99% of the animals used in experimentation² from enforceable regulations define the reality of animal use in U.S. laboratories.

The federal Animal Welfare Act (AWA) and the Health Research Extension Act of 1985 (HREA) are the only two federal laws that provide minimal standards for the treatment of animals in U.S. laboratories. Both laws are deficient, and critical issues hinder their effectiveness.

The vast majority of animals used in laboratories in the U.S. are not covered by the AWA. This includes approximately 111 million rats and mice³ and millions of fish, horseshoe crabs, frogs, cephalopods, turtles, purpose-bred birds, and other animals bred for food and fiber who are not recognized as “animals” under the law.⁴ Meanwhile, the HREA only applies to institutions receiving taxpayer funding from U.S. federal health agencies, such as NIH,⁵ leaving many animals who are used in institutions not funded by NIH without any legal protection. Although some states have laws against cruelty to animals, most have exemptions that exclude animals used in experimentation.⁶

Neither federal law mandates that experimenters should not use animals unnecessarily or consider replacing animal use with a non-animal approach, only that they have considered alternatives to specific harmful procedures they plan to carry out. Even then, the requirement to search for less harmful or distressing procedures is not reliably enforced.

Improving oversight would reduce substantial harm to animals, but it wouldn’t solve the problem. A shift away from animal use entirely would eliminate the need for more stringent regulation of animal use and protect the well-being of both humans and other animals.

Rubberstamping: Institutional Animal Care and Use Committees

Established in response to the public outcry over cruelty cases involving animals in laboratories, Institutional Animal Care and Use Committees (IACUC) were established with the intent to ensure that institutions using animals in experimentation adhered to the AWA. It was expected “that bodies such as [these] ethical committees will take corporate social responsibility by acting as watchdogs for animal experiments”⁷

In practice, IACUCs lack the essential ethical and scientific diversity to effectively address growing concerns about animal welfare and the ability to avoid animal use.⁸ A 2012 study documented that, on average, IACUC membership at top NIH-funded institutions was dominated by animal experimenters. The authors wrote that the “overwhelming presence of animal research and institutional interests may dilute input from the few IACUC members representing animal welfare and the general public, contribute to previously-documented committee bias in favor of approving animal experiments and reduce the overall objectivity and effectiveness of the oversight system.” ⁹

Ambiguous legislative language and poor oversight by IACUCs have led to inconsistencies in implementation and effectiveness. Multiple Office of the Inspector General (OIG) audits and internal surveys have demonstrated the weakness of IACUCs:

• In 1995, the OIG found that IACUCs failed to ensure that experimenters had looked for alternatives to harmful procedures or that the proposed studies were not unnecessarily duplicative of previous experiments.¹⁰
• A 2000 U.S. Department of Agriculture (USDA) survey of the agency’s laboratory inspectors showed that the biggest problem area for IACUCs was the search for alternatives to painful procedures, revealing that “600 to 800 facilities have had trouble with the search for alternatives.” USDA inspectors also felt that “undue influence” of principal investigators was a problem for IACUCs.¹¹
• A 2005 OIG audit report again highlighted these issues, noting ongoing “problems with the search for alternative research, veterinary care, review of painful procedures, and the researchers’ use of animals.”¹²
• Problems with IACUCs remained a prominent feature of OIG’s 2014 audit report, which warned that IACUCs “are not always adequately monitoring experimental procedures on animals,” resulting in “reduced assurance that protocols are properly completed, approved, and adhered to and that animals are always receiving basic humane care and treatment.” The data agreed: Between 2009 and 2011, USDA inspectors cited 531 facilities for 1,379 violations due to IACUCs’ failure to adequately review and monitor the use of animals.¹³

But little is changing. The most recent NIH initiative to enhance both rigor and reproducibility in research failed to address the myriad issues with IACUCs and their review processes.¹⁴

A major failing of U.S. oversight of experiments on animals is that there is no point within the protocol approval process where the harm that will be endured by animals is weighed against the expected benefits of the research. While oversight bodies claim adherence to policies that require the performance of a harm-benefit analysis,¹⁵¹⁶ the bodies that perform the assessment of harm are separate from those assessing benefit, and there is no attempt to balance the results. IACUCs review the harm that will be inflicted on AWA-covered animals or animals involved in NIH-funded protocols, while funding committees are tasked with considering how the experiments might benefit the field. The two committees operate disparately, don’t share their opinions with one another, and render binary judgements, resulting in a fragmented and incomplete evaluation system.

The 3Rs Are Insufficient

The 3Rs—the replacement, reduction, and refinement of animal use—have been the longstanding ethical framework guiding the use of animals in biomedical research around the world. Introduced by William Russell and Rex Burch in their 1959 book The Principles of Humane Experimental Technique,¹⁷ the 3Rs have faced significant criticism in recent years for their failure to prevent unnecessary harm to animals due to their narrow focus on procedural ethics, rather than addressing broader societal and moral questions surrounding animal research. Some scholars argue that the principles do not adequately encompass the complexities of animal welfare and ethical considerations in research.¹⁸¹⁹²⁰ Others posit that though the 3Rs may have been fit for their time, science has advanced significantly since their inception, necessitating a modern update.²¹²²²³

What is clear is that the 3Rs have not been successful. Counter to the principles of reduction and refinement, more animals are used in experimentation now than when the 3Rs concept was published^24252627 and they continue to be used in procedures that are distressing and harmful. The establishment of 3Rs centers around the globe²⁸ has not effectively curbed the use of tens of millions of animals in experiments, nor has it stopped animals from being used in experiments that have little chance of generating tangible benefits for human health.