Tending Adam's Garden : Evolving the Cognitive Immune Self

Features

• Cover Type: Paperback with 296 pages
• Published by: Academic Press
• Edition: 1st Edition August 10, 2004
• Written in: English
• ISBN 10 Number: 0121783561
• ISBN 13 Number: 978-0121783563
• Book Dimensions: 8.9 x 6 x 0.6 inches
• Weighs: 1 pounds

From The New England Journal of Medicine
Immunology is in crisis. Despite advances in the knowledge of molecular mechanisms and therapies made in the past 25 years, the structure of the theory that has guided the discipline since the 1950s is collapsing. Irun Cohen, a leading experimental and theoretical immunologist, is one of the prophets who clearly sees the limits of current dogma and who has the vision to propose new alternatives. Not content with continuing his argument with fellow immunologists alone, he designed his book for a wide readership.

Tending Adam's Garden can be roughly divided into two parts. The first half serves as background for Cohen's alternative concept of immune function: a dynamic, self-organizing system devoted to cognition. With this general introduction, Cohen, in the second half, sketches a portrait of the immune system and autoimmunity, emphasizing causation, cognition, and complexity, in an attempt to replace the existing concepts. Beyond the philosophy and polemics, Cohen offers a creative and provocative reading of contemporary immunology, one that may well guide the discipline as it seeks solutions to its paradoxes, and he creates models for restoring its increasingly complex components into a coherent whole.

The focus of Cohen's critique is the clonal-selection theory, which was originally proposed by Sir Frank Macfarlane Burnet and is the governing model of immunology. But this theory, which some orthodox textbooks have referred to as a fact, can, in Cohen's words, "no longer account for what we have learned about the immune system." The basic precept of the clonal-selection theory -- the specificity of self-antigens and the discrimination between them and foreign antigens -- does not hold. The theory's notion that there exists a one-to-one correspondence between an antigen and its receptor ignores the essential lessons of contemporary immunology: The meaning of a given antigen is governed by the complex interplay of the endogenous and exogenous factors in which it appears. What Cohen calls specificity -- the particular meaning of an antigen (is it self or foreign?) -- is determined not by its intrinsic character, but rather by the context of its presentation. The idea that an antigen is either self or nonself is lax and ultimately inadequate because of the degeneracy (nonfidelity of perception), pleiotropism (the diversity of effects), redundancy, and randomness of immune receptors. Cohen asks, "How can the system generate specificity out of the basic non-specificity of its component parts?"

The answer Cohen offers requires thinking about the immune system in a radically different way. Cohen is one of the principal proponents of a contextual theory of immune function, which asserts that the components of the immune system mutually respond to the antigenic world by forming regulatory networks. Macrophages, T cells, and B cells reinforce and modify their diverse views of the world and thereby forge an intricate network of cytokines, antigen receptors, and antibodies in a self-regulating lattice. Working in parallel, the major cellular components note different features of any target (host or foreign) and, after making their respective observations, report their characteristic findings to the other components. In other words, "the immune system responds to its own response." As Niels Jerne argued in the 1970s, it is the pattern of cognition, not some simple on-off switch, that is critical for responsiveness. So, just as the cones of the retina can sense only three colors, so too do three types of immunocytes give rise to a cognitive system that perceives, processes, and acts on information. The seeming defects of the lack of a one-to-one specificity of antigen and receptor is, according to Cohen, the "solution" to immune behavior. In his scheme, degeneracy and pleiotropism become the essential characteristics of the construction of immune patterns. In short, "immune specificity is not a given; it is a construction." It is a short step from this postulate to the idea that nothing is intrinsically foreign or native: only the context designates the character of an antigen.

Cohen's views relate directly to his concept of autoimmunity, which "is not an aberration, as taught by the classical CST [clonal-selection theory], but is at the heart of the immune system." For Cohen, the immune system is organized around key self-antigens, the so-called immune homunculus, a schematic signature of the self that serves as the organizational point of immune function. For Cohen, the immune system is constantly sensing these self-antigens and thereby governs the integrity of the organism (an idea first proposed in a different form by Elie Metchnikoff more than a century ago). The foreign is "seen" with that antigenic lexicon, and reaction occurs when the pattern of sensing self is disturbed. In this scheme, Cohen has retained Jerne's essential theoretical point: the immune system can only know itself, and thus autoimmunity is intrinsic to the behavior of the normal immune system. Autoimmune disease is the disregulated state of this normal surveillance, and Cohen argues that the treatment of autoimmune diseases should be directed at reestablishing the homeostatic balance of autoimmunity. He believes that the clonal-selection theory will ultimately be overturned because its therapeutic approach -- abolishing autoimmune clones -- has failed, and the success of reactivating or balancing autoimmunity will confirm the cognitive concept.

Cohen has attempted to undercut the complacency of a discipline that at times seems excessively satisfied with its own achievements and expectations. He challenges the clonal-selection theory but aims even higher: Tending Adam's Garden is an ambitious statement about biology, and like Gerald Edelman's Neural Darwinism: The Theory of Neuronal Group Selection (New York: Basic Books, 1987) or Richard Dawkins's The Selfish Gene (New York: Oxford University Press, 1976), it seeks to establish a new vision, a different way of conceiving the organism. Cohen is fundamentally concerned with our attraction to oversimplified models of life processes that are based on linear mechanical causation. He would have us think instead of the system as a whole -- its informational character and developmental properties and the complex self-organizational dynamics required to explain these characteristics. In this sense, immunology is a particular example of more general complex biologic systems. The ultimate success or failure of Cohen's concepts will depend on many factors beyond his control or prediction, but at the very least he may be satisfied with, and we may be grateful for, the cogency of his argument and the creative insight he has offered into the nature of immunity, the organization of its function, and the promise of therapeutic approaches based on new ways of thinking. He has provoked us to question the basic assumptions of immunology; I believe he has done more, by showing us the shape of its future.

Reviewed by Alfred I. Tauber, M.D.
Copyright © 2000 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS. --This text refers to the Hardcover edition.

Product Review
"written in clear and non-technical language, and different audiences may find it relevant for their own fields of interest." -- Dr. Yair Neuman, Ben-Gurion University of Negev, for Systems Research and Behavioral Science, June 2002

"As one might have expected from such a sophisticated person, the book is very clearly written and elaborated, very attractive and full of original concepts on immunology and neurobiology. The author's international reputation is outstanding and the text has been the matter of extensive thinking and care by an obviously gifted writer." -- Jean-Francois Bach, Necker Hospital, Paris

"Cohen's book is a wonderful journey into the world of the immune system. The writing is original, provocative and touches on more than immunology, it touches on science itself." -- Howard L.Weiner, Harvard Medical School

"I consider the whole book to be quite brilliant The whole book, including of course the second half (On Immunity) should be compulsory reading for all immunologists." -- Graham Rook, University College London

"It ranks among the best dissertations on natural philosophy that I have ever read. Aristotle would be bemused and Darwin delighted." -- Gene H. Stollerman, M.D., Professor of Medicine and Public Health, Emeritus, Boston University

"It's TERRIFIC. Very clear, very well written, without a trace of clich or second-hand thought. And amusing, full of good jokes and poetical statements." -- N. Avrion Mitchison, University College London

"Tending Adam's Garden is an ambitious statement about biology and like Richard Dawkin's The Selfish Gene, it seeks to establish a new vision,a different way of conceiving the organism."
- The New England Journal of Medicine

"The book is gorgeous, as I suspected it would be, full of deep thought and philosophy. We are in need of your visions."
- Alex Whelan, St James Hospital, Dublin

"It's TERRIFIC. Very clear, very well written, without a trace of cliché or second-hand thought. And amusing, full of good jokes and poetical statements. Most important, it seems to me to be true "
- Av Mitchison, University College London

"Putting my reservations aside, I can recommend Tending Adam's Garden highly to laypeople and scientists alike, whether they are knowledgeable about immunology or not, as one way into the immune system."
- Charles A. Janeway, Jr., Immunobiology, Yale University School of Medicine on American Scientist Webpage -- Review

"The book is gorgeous, as I suspected it would be, full of deep thought and philosophy." -- Alex Whelan, St James Hospital, Dublin

"[Professor Cohen] has created a brilliant and iconoclastic text, that well-reflects his own broad intellectual foundations. His novel ideas will be provocative for scholars and lay persons alike." -- Martin J. Blaser, Director, Division of Infectious Diseases, Vanderbilt University

"without a question a special bookfull of insights and felicitous comparisons and analogies." -- SCIENCE, July 2001 --This text refers to the Hardcover edition.

Reader Reviews
In this book the author makes a seemingly radical hypothesis, namely that human immune system is in fact a cognitive system. Those who think of a cognitive system as also being one that is conscious will find the author's contention perhaps even more radical. However, the author's notion of a cognitive system is not as elaborate, and such systems are very prevalent in manufacturing and control systems, telecommunication networks, and military systems. The book is targeted toward a wide readership, and therefore the author omits detailed scientific jargon and also omits many references. Readers (such as this reviewer) who are not experts in immunology though can still gain a lot of insight into the workings of the human immune system, and the book could be read as an introduction to this important field. In fact, a non-expert in immunology might gain much more from the book than an expert, for the former has not been biased by the "classical" clonal selection theory of the immune system, and will therefore be more open to the prospect of a different paradigm. The physicist/mathematician reader will find an interesting use by the author of chaotic dynamical systems and its notion of an attractor. The use of these concepts goes along with the author's notion of evolution and adaptation, which he describes as a radical departure from the standard view. Adaptation, in his view, is defined as an attractor, and is not correlated with improvement of the organism. Evolution does not involve the `improvement of DNA' but rather is the `creation and occupation of attractors.' The main virtue of this book is the author's careful elucidation of the notion of a cognitive system. This is necessary in his view in order to distinguish such a system from one that might qualify as being cognitive, but one would not want to view as being cognitive. As evidence of the latter, he gives the example of the production of urine by the kidneys. Such a system he says exhibits complexity, precision, and regulation that rivals many nervous systems, but one that should not qualify as being cognitive. A cognitive system he argues is able to make decisions, is able to form images of their environments, and is able to learn from experience. This learning ability involves the updating of their internal structures and images, which the author refers to as `self-organization.' Hence `choice,' `internal images,' and `self-organization' allows the cognitive system, and therefore the organism that possesses it, to interact with the world that will give it distinct advantages over what can be obtained from evolutionary genetics. So what is the nature of the `images' of the environment encoded by the immune system? They are merely proteins, some of which are distributed throughout the body and form geometrical shapes as well as `abstract, functional' ones. These images are also of two types, the `innate' images, which are inherited, and `acquired' images, which arise from the cognitive process. Autoimmune diseases, the author argues, involve an image dysfunction in the immune system. A cognitive view of the immune system the author thinks is necessary because of the need for immune receptors to have the ability for specific recognition. However, they are degenerate, `pleiotropic', redundant, and random observes the author, and this means that cognition (as he defines it) is necessary in order that the immune system generate specificity out of the non-specificity of its components. The author outlines in detail how to construct immune cognition, this involving the `geometry' of cognition, the `dynamics' of cognition, and the `images' or `patterns' of cognition. In terms of its ability to engage in cognitive decision-making, the immune system reacts to a pattern of signals that it receives by selecting a particular type of response pattern from its collection of available responses. An `immune language' that combines germ-line and somatic `chemical words' is used to make the decisions. These choices, the author emphasizes, are not the result of any `self-reflective consciousness' or `mystical free will' but in fact are deterministic. Choices in the immune system can occur because it can exercise options and because it can learn. From a chemical perspective, the decision-making in the immune system involves associating somatic perceptions of objects with classes of effector responses in the germ-line. These views of immune system decision-making are fascinating, and will certainly invoke strong reactions from the philosophical community. Indeed, what is normally thought of as capabilities only found in a `mind,' namely that of abstraction, semantics, and context, these can also be found in the human immune system. It communicates via molecular interactions; its antigens and cytokines express semantic attributes since they can confirm ligands and their receptors and can arrange the signal molecules in patterns; and can patterns of signals can create a signal context. The immune system can be defective, this resulting among other things in the deadly autoimmune diseases. The author discusses this unfortunate circumstance in detail in the book, but he is also willing to contemplate deliberate intervention into the workings of the immune system in order to circumvent any problems with it. In the last paragraph of the book, noting that "two cognitive systems are better than one," the author advocates the deliberate engineering of the immune system, i.e. that of turning "on or off the immune response as we see fit." Along with genetic engineering, metabolic engineering, and other endeavors of twenty-first century technology, such a prospect is awesome.