Model Systems in Biology: History, Philosophy, and Practical Concerns

Model Systems in Biology: History, Philosophy, and Practical Concerns 150 150 IEEE Pulse

Edited by Paul H. King
By Georg F. Strietder, MIT Press, 2022, ISBN: 978-0-262-04694-7 (Hardbound), xiii +294 pages, $45

Georg F. Striedter is a professor of neurobiology and behavior in the School of Biological Sciences at University of California at Irvine, Irvine, CA, USA. His career-long research interest “in the evolution of vertebrate brains and behavior” has led him to accept “the challenge of synthesizing experimental data that are already published” (quotes from his personal website, 

The proliferation of “the vast amount of information that we are accumulating” (Preface) juxtaposed with the declining rates of regulatory approval of drugs, particularly for cancer and neurological disorders, present existential crises to the biomedical and translational research communities (Chapter 1). Striedter attributes much of this current crisis to difficulties in the choice and use of appropriate biological modeling systems. His focus throughout the book is on the application of material models, “physical entities that are analogous to the target system in important respects” (Chapter 2), to human health and disease. He leads the reader through a discussion of the philosophy of biological modeling (Chapter 2), and histories of animal models (Chapter 3) and in vitro models (Chapter 4). Two later chapters turn to model-assisted studies of categories of commonly-occurring human disease (infectious diseases, cardiovascular disease, and cancer, Chapter 5), and neurological disorders (Chapter 6), for which progress in treatment is distressingly slow.

Chapter 7 concludes with recognition of difficulties in choosing whether and what to model, challenges of study design, and how to balance concerns about animal welfare with those for sick humans. Suggestions include the adequate design of preclinical studies and the ability to publicize failures and nonsignificant findings. Recommendations include: knowledge of material models (animals and cells) beyond “materials and methods”; judicious use of standardization; learning from clinical trials failures; embracing diversity; and learning from complexity. As an investigator once said, “The easy things have all been done,” but difficult tasks are still worth doing.

Recent scientific and technological developments have helped make model targets more accessible and more appropriate. For example, the work of medical geneticist Victor McKusick and others led to the identification of thousands of rare diseases and the establishment of the National Organization of Rare Disorders. The Human Genome Project and the decision to make its results open led to the advent of personalized medicine and the ability to store genetic information for free public access. The development of CRISPR-Cas9 technology, for which the 2020 Nobel Prize in Chemistry was shared by Doudna and Charpentier made gene editing feasible. 

Egregious mistreatment in the U.S. of Native Americans, African Americans, and other racial and ethnic minorities and the Holocaust leading to adoption of the Treaty of Helsinki, the Belmont Report, and the establishment of Institutional Review Boards have contributed to improved safety and efficacy in material model-assisted, preclinical, and translational studies.

How do animals survive in difficult environments? In a FASEB meeting  in the early 90s, renowned comparative physiologist Knut Schmidt-Nielsen, this reviewer’s mentor, told the young investigators in the room “YOU are the endangered species!,” for many of the reasons Striedter has superbly identified and discussed 30 years later.

Schmidt-Nielsen’s father-in-law August Krogh, 1920 Nobel laureate in Medicine or Physiology, cited extensively in this book, once observed: “A considerable part of my work was done in bed during the night when I would try to visualize the processes studied and the experiments to be carried out. I found that I could visualize fairly complicated apparatuses and all details of their working. The constructive ideas would come, apparently, out of nowhere, but the visionary examination of them was a conscious and rational affair.” Conceptual modeling, whether it is visualizing a series of biological experiments, contemplating experiments done by others, or crossing a traffic-congested street, is endemic to humans.

In conclusion, Striedter’s book is not one to be relegated to the coffee table. It is a well-organized, extensively referenced, thought-provoking volume replete with relevant, and up-to-date details in virtually every sentence. It is highly recommended not only for young investigators but also for experienced biomedical and clinical scientists, to be returned to and savored again and again <

Reviewed by Jerry C. Collins
Alabama A&M University