A white lab mouse stands on its hind legs and peers out of a cage at a scientist's hand.

Mice and other small animals are often used to test new drugs, but organoid technology may replace them soon.

credit: istock/Olena Kurashova

Animal testing might go, but not today

Legislation now allows some drugs to skip animal testing, but it’s unclear when, if ever, this step will be gone for good.
Dan Samorodnitsky
| 3 min read
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In late December, President Joe Biden signed the FDA Modernization Act 2.0, which allowed drugs to be approved by the Food and Drug Administration (FDA) without requiring animal testing. The move was hailed by animal rights advocates as a crucial victory, but the reaction in the biopharma space was mixed.

Animal testing provides a crucial check for drug efficacy and mammalian safety, but even after testing, many drugs fail in human trials because they don’t reach therapeutic endpoints, or they produce adverse effects (1). This results from biology’s complexity; something that is safe and effective in one organism may behave differently even in closely related organisms. 

Although the Act leaves alternative testing methods to the FDA, many scientists pointed to organ-on-a-chip and organoid technologies as logical replacements for animal testing. With these robust technologies, researchers are already testing drugs and searching for drug targets in organoids derived from tissues as far afield in the body and varied in use as the bladder, the prostate, the intestines, and even the inner ear (2–5). 

Organoids that perform adequately in toxicity testing exist for these tissues and a few others, but their uses are limited. The models excel at testing antitumor medications while avoiding the need for grafting or inducing tumors in animals (6). Organoids and chip-based models enable testing skin treatments and modeling nicotine poisoning in the brain. In vitro drug testing can’t cover everything, however. For example, a 2020 review of female reproductive organoids bluntly stated that even robust three-dimensional models are too genetically and physically distinct from an actual human uterus to do trustworthy drug safety screening (7). 

So far, these technologies haven’t proven that they reliably predict drug safety and efficacy in humans more often than animal testing does. And while they give insights into the responses of certain tissues, they lack the full context of other tissues in an organism that animal testing provides. Even with anticancer drugs, where organoid testing has been most successful, the lack of associated stroma and immune systems is a hindrance (8). On top of that, the infrastructure for creating drug testing-ready organoids is also decades behind animal testing, which has been in use in the United States since the middle of the 20th century.

The first drug to go directly to human trials without animal testing will be a landmark. In a perfect world, animal testing may not exist. The good news is that world might arrive in the near future. Hopefully, organoids will replace animals someday, but it likely won’t be soon. 

References

  1. Fogel, D. B. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review. Contemporary Clinical Trials Communications  11, 156–164 (2018).
  2. Medle, B. et al. Patient-Derived Bladder Cancer Organoid Models in Tumor Biology and Drug Testing: A Systematic Review. Cancers  14, 2062 (2022).
  3. Van Hemelryk, A. et al. Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing. Biomolecules  11, 1572 (2021).
  4. Yoshida, S., Miwa, H., Kawachi, T., Kume, S. & Takahashi, K. Generation of intestinal organoids derived from human pluripotent stem cells for drug testing. Sci Rep  10, 5989 (2020).
  5. Munnamalai, V. & Fekete, D. M. Building the human inner ear in an organoid. Nat Biotechnol  35, 518–520 (2017).
  6. Caipa Garcia, A. L., Arlt, V. M. & Phillips, D. H. Organoids for toxicology and genetic toxicology: applications with drugs and prospects for environmental carcinogenesis. Mutagenesis  37, 143–154 (2022).
  7. Heidari-Khoei, H. et al. Organoid technology in female reproductive biomedicine. Reprod Biol Endocrinol  18, 64 (2020).
  8. Drost, J. & Clevers, H. Organoids in cancer research. Nat Rev Cancer  18, 407–418 (2018).

About the Author

  • Dan Samorodnitsky
    Dan earned a PhD in biochemistry from SUNY Buffalo and completed postdoctoral fellowships at the USDA and Carnegie Mellon University. He is a freelance writer whose work has appeared in Massive Science, The Daily Beast, VICE, and GROW. Dan is most interested in writing about how molecules collaborate to create body-sized phenomena.

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April 2023 Issue
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