New scientific methods may one day replace animal studies in research laboratories, according to Clive Svendsen, PhD, executive director of the Board of Governors Regenerative Medicine Institute at Cedars-Sinai. Svendsen is working on New Approach Methodologies (NAMs), which are starting to change how biomedical research is conducted.
There are three main types of NAMs: organoids, organ-on-chip technology, and computational or “in silico” models. Organoids are small clusters of human cells that can imitate some functions of full organs. These are often grown from induced pluripotent stem cells (iPSCs), which are adult human cells reprogrammed to become any cell type and can be replicated indefinitely.
Organ-on-chip models involve growing iPSC-derived organ-specific cells on specially designed chips that simulate fluid flow and other conditions found in actual organs. Researchers have started linking different types of organ chips—such as brain, heart, and liver—to replicate more complete human systems.
In silico models use artificial intelligence tools applied to large databases of human and animal data. These tools help forecast how a drug might work or whether it could be toxic by analyzing data from similar drugs already tested in animals or humans.
Svendsen explained why animals, especially mice, have been used for medical research: “Mice and other animals provide us with a living physiological system with organs and circulation, which is something we haven’t been able to fully replicate in a laboratory dish. They also breed and age quickly, and we have learned to genetically engineer them to mimic many human diseases and conditions.”
However, there are drawbacks to using mice as stand-ins for humans. According to Svendsen: “Mouse biology and human biology are different in some important ways, including at the molecular level. In one recent case, we were studying a rare disease in children that hinges on a missing gene. When we attempted to create mice with this same disease by ‘knocking out’ that gene—nothing happened. The mice did not develop the disease. It turns out that mice have another gene with very similar functions that is missing in humans. There are millions of genetic differences between mice and humans, and the smallest one can make a huge difference.”
Of the alternative approaches being developed, Svendsen noted: “In silico is probably farthest ahead because AI is moving so quickly and we have so much data. Investigators who want to test a new drug can apply AI tools and plug the drug into large publicly available databases to learn how cells might react to that drug. And investigators who have discovered a genetic pathway that is potentially involved in a disease can plug the changes they observed into these databases to determine which drugs might reverse those changes.”
On whether these new methods can fully replace animal studies now, Svendsen said: “We are entering a transition period where these new technologies are starting to be used to enable new drug development.These technologies are very, very new and there are only a few examples of where they have been successfully used as an alternative to laboratory animal research. However, with many exciting studies on the way, this is set to change in the near future. Stay tuned!”
For now, he recommends combining both traditional animal models with newer methods: “Right now, combining some of these new methods with animal models is the best option. A laboratory animal is a complete living specimen. An organoid or organ chip offers actual human biology. And combining AI technology, animal models and organoids to test the same theory about how an organ works, how it goes wrong or how it may react to a new drugwill ultimately be incredibly powerful. If all three approaches agree, you have a much greater chance of discovering something important for human health.”
He added: “Simultaneously, we will continue to study and test whether the new methods can provide more accurate information about human biology than laboratory animals can. I believe they eventually will, because we’re constantly refining and improving NAMS technology. Ultimately, this will also provide a way to tailor our treatments to individuals as we can generate their organoids or organ chips, discover successful drug interactions, and then administer that drug to the same patient.”
Cedars-Sinai Medical Center has played an important role in advancing biomedical research since its founding in 1902 in Los Angeles https://www.cedars-sinai.org/. The hospital’s president is Thomas M. Priselac; it operates as both a treatment center—with over 50,000 patient admissions reported for 2022—and as a training hospital with specialized wards including pediatrics.
