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Many areas of biomedical research focus on the study of human-specific diseases and medical concerns. Induced animal models are rarely scientifically relevant to these studies, due to species-specific differences in anatomy, biochemistry, physiology, pharmacokinetics, and toxic responses. Use of alternative methods, especially incorporating human cells and tissues, avoids such confounding variables.
A Success StoryA specific example of a basic research alternative method, and one that potentially has saved up to one million animals, is the in vitro production of monoclonal antibodies (MAbs), which are used in nearly every field of biomedical research and critical areas of clinical practice. The widely-used ascites method of producing MAbs involves injecting cells into rodent abdominal cavities. It is extremely painful. AAVS filed a petition with the National Institutes of Health (NIH) in 1997 requesting that the agency prohibit its researchers from using the ascites method to produce MAbs. This petition paired with a scientific workshop sponsored by AAVS affiliate, the Alternatives Research & Development Foundation (ARDF), that illustrated international support for in vitro production of MAbs. As a result, the NIH changed its policy to state that its researchers, and those who receive funding from NIH, must use in vitro alternatives as the default method for MAb production.
Alternatives Used in the US
- I-MAb Gas Permeable Tissue Culture Bags are used to produce monoclonal antibodies for research diagnostic and clinical purposes. Developed by the ARDF, could replace up to one million mice a year.
- National Library of Medicine Visible Human Project utilized actual human cadaver cross-sections, CAT scans, and computer programs to develop new surgical techniques and research perspective.
- Organotypic cultures of human brain slices are used to study neurobiochemistry, neurophysiology, and drug efficacy.
- Short, direct non-invasive magnetic pulses allow precise stimulation of brain cells/regions in human volunteers for neurosciences.
- Use of mathematical models and computer simulations in physiology, cardiovascular, pharmacology, and neurosciences (e.g., neural networks).
- Use of non-invasive functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to study neuroanatomy and neurophysiology in human patients and volunteers.
- Use of three-dimensional human cell cultures to study drug penetration and characteristics of the blood-brain barrier.
- Use of echocardiography, color-coded dopler imaging and abdominal sonography as non-invasive methods for cardiovascular research in human patients and volunteers.
- Use of normal and pathological human cell and tissue cultures to identify disease processes and treatments.
- Use of three-dimensional bioengineered human skin cultures to study effects of burns and ultraviolet exposure.