HMN 2026: What is the Innovative pathway in biomedical research

New scientific methods could one day render animal studies—the standard in research laboratories for more than 100 years—obsolete. Clive Svendsen, Ph.D., executive director of the Board of Governors Regenerative Medicine Institute at Cedars-Sinai, is helping to pioneer New Approach Methodologies (NAMs), which are beginning to change research practices.

There are currently three types of NAMs: organoids, organ-on-chip technology, and computational, or “in silico,” models.

In an editorial published in Cell Stem Cell, Svendsen discusses the promise and challenges surrounding these methods. He shared some of his thoughts with the Cedars-Sinai Newsroom.

How do the various new approaches work?

Organoids are small bundles of human cells that can mimic some of the function of complete organs. While they can be generated from some adult human organs such as the gut, these adult organoids often have limited potential for cultivation and replication.

Instead, we grow organoids from induced pluripotent stem cells, or iPSCs, which are mature adult human cells that have been reprogrammed into a state where they are immortal, can be replicated indefinitely and can become almost any cell type.

In organ-on-chip models, iPSC-derived organ-specific cells are grown in specially designed chips that mimic fluid flow in the body and replicate conditions cells would experience in an actual organ. In some cases, investigators are linking different types of organ chips—brain, heart, liver—as a way to replicate a complete human system.

With in silico models, AI tools are applied to large databases of human and animal data. These tools allow us to forecast how a drug works or whether it’s toxic, based on data from similar drugs that have already undergone animal or human testing.

Why do we use animals, particularly mice, 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.

What is the downside to mice as a stand-in for humans?

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.

Which of the alternative approaches is most developed?

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.

Are we ready to make the leap from animal studies to these new scientific methods?

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!

What should we do in the meantime?

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 drug will ultimately be incredibly powerful.

If all three approaches agree, you have a much greater chance of discovering something important for human health.

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.

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