The Flaws of Standard Mouse Models in Scientific Studies
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The Flaws of Standard Mouse Models in Scientific Studies

Ari Horesh


The world of scientific research, especially in biomedical fields, often relies on animal models, particularly mice, to conduct experiments that cannot be ethically or practically performed on humans. This article delves into the critical insights from Peter Attia and Rich Miller discussing the significant limitations of standard mouse models in research, specifically focusing on the C-57 Black Six (B6) mouse model, and the need for more genetically diverse models.

The Problem with Homogeneity

Standard Mouse Model: The Black Six

The standard mouse model used in research is the Black Six mouse. These mice are inbred, meaning they have a homogeneous genetic makeup. While this might seem advantageous for controlled experiments, it presents a major flaw: lack of genetic diversity.

"If you have a drug that works in Black Six mice, it might work in another kind of mouse; it might not work; it might have the opposite effect in another kind of mouse." - Rich Miller

Issues with Inbreeding

Inbreeding in mice, much like in humans, leads to a plethora of health issues. Most inbred mice are prone to diseases, deafness, and other health problems, which aren’t representative of a general population.

Implications for Research

Using such a homogeneous group for research is analogous to testing a drug on a set of identical triplets and expecting it to work the same way in a genetically diverse population. This lack of diversity often leads to misleading results in biomedical research.

A Better Alternative: Heterogeneous Models

The UM-HET3 Mouse Model

In contrast to the Black Six model, the UM-HET3 mouse model offers a form of "reproducible heterogeneity." These mice share half of their genes with a random assortment, much like human siblings. This model provides a more realistic scenario for testing drugs and understanding genetics.

"No two mice are identical, but all populations of UM-HET3 genetically are identical with one another." - Rich Miller

Advantages of Genetic Diversity

  1. Reduced Genetic Anomalies: Less likelihood of unusual genetic traits skewing results.
  2. Increased Relevance: More applicable to a diverse human population.
  3. Gene Mapping Potential: Allows for better understanding of specific genes related to lifespan and diseases.

Why the Persistence with Black Six?

Tradition and Limitations

Despite its flaws, the Black Six model persists, primarily due to tradition in the scientific community and limited resources. Researchers often stick to familiar models due to mentorship influence or financial constraints.

"It's like lemmings; you follow the lemming in front of you." - Rich Miller

Appropriate Uses for Inbred Mice

While not ideal for all research, inbred mice can be useful in studying specific diseases or for transplantation studies. However, their utility is limited and should be carefully considered in the context of the research objective.

Conclusion: A Call for Change

The conversation between Peter Attia and Rich Miller underscores a crucial need for change in biomedical research methodologies. Embracing genetically diverse mouse models like the UM-HET3 could lead to more accurate, reliable, and relevant results in scientific studies. This shift is not just a matter of scientific accuracy but also of ethical responsibility towards producing research that truly benefits a diverse human population.

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