In search of Spallanzani's dream


REGENERATIVE BIOLOGY AND MEDICINE David L. Stocum Academic Press–Elsevier, Burlington, MA, 2006, 448 p, $69.95 ISBN 13: 978-0-12-369371-6 ISBN 10: 0-12-369371-3

Shannon J. Odelberg*, * Department of Internal Medicine, Division of Cardiology, University of Utah, Salt Lake City, Utah.

But if the above-mentioned animals, either aquatic or amphibious, recover their legs, even when kept on dry ground, how comes it to pass, that other land animals, at least such as are commonly accounted perfect, and are better known to us, are not endued with the same power? Is it to be hoped they may acquire them by some useful disposition? and should the flattering expectation of obtaining this advantage for ourselves be considered entirely as chimerical?

Lazzaro Spallanzani, 1768 (translated from Italian in 1769)

That certain animals can regenerate lost structures and injured organs has fascinated humans for more than two millennia. The ancient Greeks constructed myths regarding regeneration, including one in which the nocturnal regeneration of Prometheus's liver provided daily nourishment to a ravenous eagle, while causing constant torment for poor Prometheus. In another tale, Heracles, as one of his assigned labors, was required to kill the greatly feared nine-headed monster named Hydra. He accomplished this task by decapitating each head and cauterizing the stump before two new heads could regenerate in place of the original head. Aristotle (384–322 B.C.) noted in his Historia Animalia that lizards could regenerate their tails. But only in the eighteenth century did natural philosophers begin to study regeneration using the scientific method. In 1712, the French scientist René-Antoine Ferchault de Réamur first described regeneration of claws and legs in crayfish. By the end of the eighteenth century, several scientists, including Abraham Trembley, Charles Bonnet, Peter Simon Pallas, and Lazzaro Spallanzani, had carefully examined the regenerative abilities of hydra, annelid worms, flatworms, salamanders, frog tadpoles, and snails. Spallanzani closed his classic An Essay on Animal Reproductions by pondering whether humans would ever gain the ability to regenerate lost limbs, as do salamanders and amphibious tadpoles.

With the advent of stem cell biology and the demonstration of its practical medical application in regenerating hematopoietic cells after their eradication, regenerative medicine appears to be on the brink of some major breakthroughs. However, this new science is encumbered by both scientific and ethical controversies. On the scientific side, the controversy includes the degree to which so-called adult stem cells can exhibit cell lineage plasticity. On the ethical front, the major controversy revolves around the use of human embryonic stem cells for research purposes and medical applications. Furthermore, scientists, politicians, and the public often ignore the vital importance of studying model organisms that have the natural ability to regenerate lost structures or injured organs. Nature has already provided a solution to the regeneration problem, and one approach to regenerative medicine would be to mimic the mechanisms nature has already perfected.

In Regenerative Biology and Medicine, David Stocum, who has been a leader in regeneration research for nearly four decades, directly addresses each of these issues and emphasizes the importance of tackling the problem of regeneration using a variety of approaches. The book covers a broad spectrum of research related to the biology of regeneration as well as regenerative medicine. What makes this book remarkable is not so much its comprehensive nature—many comprehensive books have been written on a variety of subjects. However, these books are often written by a team of experts with each author contributing a chapter or two in his or her particular area of expertise. What makes this book remarkable is that it is both comprehensive and written by a single author. In this regard, the book is a tour de force. That it is written by one individual has several advantages, the primary one being that the book reads as if it were a cohesive unit with a similar style of language and a uniform organization between chapters.

The book contains 15 chapters with Chapter 1 providing an overview to the fields of regenerative biology and medicine. Chapters 2 through 12 are organized according to organ and tissue systems with the biology underlying regeneration in each system being discussed in one or two chapters and the application of the science to regenerative medicine being discussed in the subsequent chapter. The systems covered include skin, dental, and eye tissues (Chapters 2–4); neural tissues (Chapters 5 and 6); digestive, respiratory, and urogenital tissues (Chapters 7 and 8); musculoskeletal tissues (Chapters 9 and 10); hematopoietic and cardiovascular tissues (Chapters 11 and 12); and appendages (Chapter 14). This approach works well and is one feature that sets this book apart from the excellent texts that have preceded it over the decades, such as Thomas Hunt Morgan's Regeneration (1901), Richard Goss's Principles of Regeneration (1969), and the multiauthored book Cellular and Molecular Basis of Regeneration—From Invertebrates to Humans (1998; edited by P. Ferretti and J. Géraudic). Of course, another feature that sets this book apart from the others is its timeliness. References are fairly up-to-date, with cited articles through at least 2005. To complete the book, the author covers the controversial area of lineage plasticity in adult stem cells in Chapter 13 and addresses current research issues in regenerative medicine in Chapter 15, including both the scientific and ethical issues surrounding adult and human embryonic stem cells.

Each chapter begins with an introduction, followed by an in-depth review of the topic, and concludes with a lengthy and fairly detailed summary. If a reader is only interested in getting a comprehensive overview of the subject, he or she can simply read the Introduction and Summary section of the particular chapter(s) of interest. Each chapter has numerous references that provide the reader with an entrée into the vast literature on regeneration or regenerative medicine.

The intent of this book as stated in its Preface is twofold: (1) to bring together under one umbrella the highly related fields of regenerative biology and regenerative medicine and (2) to provide graduate, advanced undergraduate, and medical students as well as clinical physicians and research investigators a reference text that covers the broad spectrum of regenerative biology and medicine. These goals are certainly met, although much of the material may be presented at a level that would be difficult for most upper division undergraduate students to comprehend. The book would certainly be an excellent choice for a graduate level course in regeneration and ideally would serve as a source guide to the original literature.

As noted above, that this book is written by a single individual has advantages. However, it also gives rise to one of its few weaknesses. It is very difficult for any one author to cover such a broad topic without errors occasionally creeping into the text. An example of such an error is the implication that the hair cells of the cochlea and utricle are part of the central nervous system, rather than the peripheral nervous system. The book also contains very little discussion of the regenerative abilities of invertebrate organisms and yet the information garnered from studying these organisms would enhance our understanding of the mechanisms of regeneration and could one day lead to regenerative therapies. The book contains a few figures of lower quality that have been reproduced from other sources. It is probable that the lower quality results from enlarging the figures beyond their original size. Nonetheless, these figures are easily interpretable and their lower quality will not confuse the reader. Finally, there are several typographical errors that should be corrected on subsequent editions of this book, although these errors can easily be recognized and do not distort the meaning of the text.

In summary, Regenerative Biology and Medicine is a welcome addition to the many excellent books on regeneration for it fills an important niche that is not currently occupied by other texts. By blending discussions of regeneration biology with regenerative medicine, it seeks to present a more complete picture of both fields. Those who study the biology of regeneration will appreciate the author's successful attempt to place regenerative medicine in context with the broader field of regeneration, while clinicians and researchers trying to enhance or induce regenerative responses in mammals through stem cell technology should gain a greater appreciation for the information that can be gleaned from studying regenerative mechanisms in animals that have natural regenerative abilities. Although the fields of regenerative biology and medicine are moving at a rapid pace, this text provides foundational information for these subjects that will prove useful for years to come. However, to remain current, this text will need to be updated often, so it is hoped that the author will consider publishing future editions of this informative book.