Feinberg Professor emerita Eva Redei’s research had two key components: vats of water and “depressed” rats. Redei found that the rodents, genetically engineered in a Kyoto lab to exhibit depressive symptoms, refused to paddle to safety after being placed in the water, instead choosing to simply float until they were retrieved.

By studying such behaviors, Redei’s lab found and measured over two dozen gene transcripts linked to depression in rats — findings which could then be translated to humans, she said. Her team laid the groundwork for identifying individuals at risk for depression, one of the world’s most prevalent and underdiagnosed mental illnesses.

However, over the decades that Redei has conducted depression studies, the federal agencies responsible for funding such research have made pronounced moves away from animal testing.

Advances in data science and artificial intelligence led the National Institutes of Health to announce an initiative in May to phase out animals in favor of “human-based” research methods like tissues on a chip, real-world data analysis and miniature lab-grown organ-like structures called organoids.

The proposed approach boils down to “3 R’s”: refining techniques to maximize animal welfare, reducing the number of animals in labs and — wherever possible — replacing animal subjects entirely.

However, Redei said she doubted the efficacy of the NIH’s proposed alternatives to animal testing.

“The danger here is that people are making these regulations without thinking through the complexity of the human body,” Redei said. “How can AI mimic the process of thought or memory, which we don’t know yet? To emphasize AI and say, ‘Therefore we don’t need animal research’ is absolutely wrong.”

As one of the top recipients of NIH funding, Northwestern’s labs contain a substantial number of animals. According to an Annual Report, the University has eight non-human primates, 51 dogs and 168 pigs used in its labs, as of 2023.

However, this likely only accounts for 5% to 10% of the animals in NU’s labs, as the rest, such as birds, rats and mice bred specifically for research, are not required to be publicly disclosed.

But federal organizations like the NIH aren’t the sole overseers of these experiments — that responsibility falls to NU’s Institutional Animal Care and Use Committee.

Comprising scientists, veterinarians, non-scientific faculty and representatives of community interests, the IACUC is responsible for finding alternatives to animal testing, enforcing regulations and minimizing both animal harm and usage. Every research university must have an IACUC, and they serve as the final layer of oversight in the federal compliance process.

Molecular biosciences Prof. Carole LaBonne, the president of NU’s Society for Developmental Biology, studies embryo development using frogs as model organisms. Since starting her NU lab in 2001, she said she has regularly navigated the IACUC review process.

Every scientific experiment involving lab animals needs an explicit animal protocol, which adds several weeks to the approval process. Furthermore, LaBonne said these proposals face intense scrutiny from federal bodies before even reaching IACUC review — a process that can take eight to 20 months.

“These committees are so afraid of not regulating enough that they’ll often tell me that I have to or can’t do something that the government doesn’t require,” she said.

For example, LaBonne said NU’s IACUC mandates that her lab track the pain categories of its frogs despite no federal requirement to do so. While she supports minimizing the discomfort of animals in her lab, LaBonne said such overregulation can add to the already steep demands on researchers’ time and funding.

In an attempt to streamline this approval process, the FDA announced in May its plans to offer case-by-case exemptions for certain drugs that demonstrate safety through valid alternatives to animal testing, which “fast-tracks” the regulatory review process for studies with minimal animal usage.

However, some critics argue that, despite such reforms, the system remains structurally slanted in favor of animal testing.

At the top 25 NIH-funded institutions, animal researchers compose up to 92.6% of IACUC chairpersons, according to an NIH study, leading to complaints that animal welfare and general public interest perspectives are underrepresented.

In extreme cases, this imbalance can lead to serious failures in oversight. In 2002, Dr. Catherine Dell’Orto, then a postdoctoral researcher at Columbia University, reported witnessing baboons undergoing induced strokes, caused by the removal of an eye and the clamping of an artery, without being given proper anesthesia.

Dell’Orto raised complaints to Columbia’s IACUC, but instead of addressing the complaints, the head veterinarian revoked Dell’Orto’s access to the baboon laboratories. Dell’Orto then contacted People for the Ethical Treatment of Animals with her allegations, which led to a prolonged advocacy effort resulting in the firing of the head veterinarian and a $2,000 fine on Columbia.

Alka Chandna worked with PETA on their 2003 Columbia campaign and now evaluates similar incidents while serving as the organization’s vice president of laboratory investigations cases. Even with IACUC’s cooperation, she said punishment from federal agencies often falls short, which can create permissive environments for ignoring animal welfare.

“The USDA often fines facilities pennies to the dollar because they just don’t have the resources to take on lawsuits from well-heeled institutions like Columbia University,” Chandna said. “Universities tend to think of these fines as just the cost of conducting business.”

Fully staffed, the USDA should have 120 inspectors according to Chandna, but they currently operate with around 100 due to lack of financial resources, Chandna said. Because these inspectors are responsible for overseeing around 15,000 facilities, 1,400 of which are laboratories, Chandna said labs often undergo perfunctory or inaccurate evaluations.

This means self-reports like Dr. Dell’Orto’s are the primary method of uncovering violations of laboratory standards, Chandna said.

While the NIH promotes human-based research as a solution to the extensive oversight necessary for animal testing, their novelty has researchers unconvinced that they could produce results comparable to those achieved through animal testing.

Weinberg junior Carson Walters has worked with fruit flies in NU’s Holmgren lab since his freshman year. Although he acknowledges the ethical concerns, he said he sees no clear replacement for animals in research.

“You can’t replicate a real living fruit fly, at least not yet,” Walters said. “By going to purely computational models, you’ll miss out on things you aren’t necessarily looking for.”

With the Holmgren lab, Walters removes different proteins from fruit flies to see how their fat cells communicate a starvation response. Several times, Walters said he observed completely unexpected results, like how removing certain proteins can cause larvae to begin crawling up the walls of their test tubes or die unexpectedly.

“Sometimes I feel bad, because we kill a lot of flies, and their whole lives are in these tubes,” Walters said. “But I really feel like this research could have findings that outweigh the deaths.”

The Holmgren lab’s research may eventually inform the study of metabolic diseases, Walters said, but these results won’t be immediate. Rather, Walters said the lab is building up foundational knowledge for other researchers to draw from, which can take years.

In addition to the time investment, Walters said considerable labor goes into the maintenance of the lab’s fruit flies. Therefore, he said new methods could save resources by complementing — not replacing — some of the existing work being done.

However, many researchers have raised concerns about the NIH’s capacity to carry out their proposed initiatives following the termination of $1.9 billion in NIH medical research grants, the firing of 1,000 NIH staffers and the Trump administration’s plan to slash the agency’s budget from $47 billion to $27 billion.

“It’s been estimated that 100% of all drugs that have been developed in the last decade were developed using animal research,” LaBonne said.
“99% of them were developed using NIH research funds. Federal funding is everything.”

The NIH has yet to announce the budget, composition or timeline for its upcoming Office of Research Innovation, Validation and Application, which is intended to coordinate the advancement of human-based research capabilities and expedite the time it takes for critical research to reach consumers.

As for Redei, despite conducting her depression experiments over a decade ago, she said she’s still waiting for its results to reach the clinic.

“It will take a long time, another 10 years or more,” Redei said. “I won’t be around, but that doesn’t matter — because it proved something.”

Email: [email protected]

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