An Elegant Defense

An Elegant Defense
Author: Matt Richtel

Background

The subject of this book is the exquisite immune system and the constellation of disorders that manifest when it fails. Describing it as ‘one of the world’s most complex systems’, the author underscored its importance when he portrayed it as ‘the glue that defines the whole of human health and wellness‘. The book painted a picture of an elegant system which is ‘precisely and delicately tailored‘ to maintain a state of harmony, and which operates efficiently to detect and disable all levels of threats. The book also conveyed the sense of the improbable task the immune system accomplishes in maintaining a delicate balance between ‘what to attack and what to leave alone’, and in restraining itself from overreacting to the invading pathogens he referred to as ‘brutal festival crashers‘. The book is also a graphic representation of the intricate signals and pathways that drive the critical activities of what is indeed an elegant defense (pages 6, 9, 43, 47, 71, 135 -139 and 153).

Immune system. Daniel Friedman on Flickr. https://www.flickr.com/photos/daniel_friedman/28347903397

Synopsis

The book’s characterisation of how the immune system wards off external and internal threats is very detailed. To illustrate the complex workings of both the innate and adaptive components of the system, the author made imaginative use of vivid metaphors, such as when he referred to neutrophils, natural killer, and dendritic cells – the first line defensive cells – as ‘constituents of a fire brigade‘; when he characterised B cells and T cells as ‘the immune system’s most advanced fighters‘; and when he referred to the tree-like tentacles that dendritic cells use to present antigens to the T and B cells. In a similar way he referred to the B cell system as a highly-evolved ‘infinity machine‘ which, pre-stocked with antibodies, has the capacity to target the rarest, the unimaginable, and the most unfathomable threats. The author also explored the other constituents of the immune system in this picturesque approach, clearly delineating the roles of such cells as macrophages, eosinophils, basophils, and monocytes. He was also similarly lucid in describing the interplay of chemical messengers such as cytokines and interleukins in triggering immune responses and generating fever (pages 46, 76-77, 90 and 114-137).

Healthy human T cell. NIAID on Flickr. https://www.flickr.com/photos/niaid/5950870236

A major theme of the book is its portrayal of the scientists who contributed most to unravelling the secrets of the immune system. In this regard, the author credited the Italian anatomist Fabricius ab Aquapendente for his pioneering insight that the bursa beneath the tail of chickens, which now bears his name, is a constituent of the immune system. The author than narrated the contributions of succeeding scientists who built on this initial discovery, and these included Elie Metchinkoff who first observed phagocytes in starfish; Paul Ehrlich, ‘the godfather of immunology’, who discovered antibodies and a range of white blood cells; Jacques Miller who fought against the scepticism of the scientific community to prove the role of the thymus gland in immunity; Max Cooper who recognised the two lineages of lymphocytes – B cells from the thymus, and T cells from the bone marrow; Susumu Tonegawa who identified the unique genes that code for antibodies; Peter Medawar who did the foundation work that enabled organ transplantation; and Kathryn Zoon who sequenced interferons – the natural chemical messengers which mediate the killing of viruses (pages 37-43, 61-65, 79, 87-97 and 129-133).

Human B lymphocyte, NAIAD on Flickr. https://www.flickr.com/photos/niaid/28942386960

A group of disorders which featured prominently in the book are the autoimmune diseases, and the author reviewed these in the contexts of their mechanisms and clinical manifestations. For example, in discussing their genesis, he stressed the hygiene hypothesis which posits that the tendency to autoimmunity is triggered in clean environments devoid of the microbes; these pathogens would otherwise have engaged the immune system and dampened their propensity to become overactive. The author also discussed the various treatments of autoimmune diseases, from methotrexate and azathioprine to etanercept and monoclonal antibodies. He also explored the historical backgrounds of some of the treatments, such as how the idea of treating lupus with steroids came about from the observation that the disorder improved whenever the sufferers came under stress – a situation that is known to trigger the production of endogenous steroids (pages 205-207, 231, 255-266 and 140-145).

Monoclonal antibody therapy. Geometric Medical Animation on Flickr. https://www.flickr.com/photos/80119778@N04/7794039994

The author’s stated inspiration for writing the book are the travails of his friend Jason Greenstein whose story of battling Hodgkin’s lymphoma ran parallel to the scientific account. The author chronicled Jason’s tortuous medical odyssey which was the result of his cancer playing ‘a nasty trick‘ on him, taking over his immune system and ‘using it to protect itself’. The narrative also depicted how Jason endured ‘four years of chemotherapy and radiation‘, braving every challenge with a determination to defy death even ‘while standing on its precipice, one foot already over the edge’. Just as the author highlighted Jason’s emotional rollercoaster of the remissions and relapses that accompanied treatment with immunotherapies such as brentuximab and nivolumab, he also portrayed the unremitting complications he endured, for example the graft versus host disease which followed his stem cell transplantation. The author also perceptively used Jason’s story to explain the complex interaction of receptors and ligands which facilitate immunotherapy, and to demonstrate how cancer cells lethally bind and activate the programmed death receptor thereby triggering T-cell self-destruction (pages 3-9, 275-276, 293-312 and 334-384).

Cancer immunotherapy. NIH Image Gallery on Flickr. https://www.flickr.com/photos/nihgov/27125551111

Besides the story of Jason, the author also recounted other touching patient narratives to illustrate the consequences of an overactive immune system. Prominent in this regard was the intriguing account of Robert Hoff whose exquisite immune system prevailed against HIV because it possessed a unique HKAB57 gene variant; on this account, Robert became a source of ‘insights and promise‘ in ‘the bedevilling search to stop AIDS‘ – a plague which the author said ‘led to a turning point in the story of immunology‘. Other patients who provided enlightening perspectives of aggressive immune systems included Linda Bowman who suffered from rheumatoid arthritis and ‘harbored inside her an invisible suicidal assassin‘; and Meredith Branscombe who was diagnosed with multiple autoimmune disorders and was depicted by the author as ‘an immune system tinderbox‘ (pages 25-31, 156-160 and 192).

HIV infected T cell. NIAID on Flickr. https://www.flickr.com/photos/niaid/6813384933

Opinion

This is a refreshing book which blends a very academic subject with a compassionate human angle. Whilst the book’s central themes are complex biological processes, the author succeeded in conveying these graphically and in simple language. Some of the patient anecdotes appeared somewhat drawn out, as was the case with Jason’s story, but this is understandably so because the author, a journalist, unequivocally set out to emphasise the human dimension of disordered immune systems. This however did not detract from what is a thoroughly scholarly exposition of a cutting edge medical field. The book is greatly enhanced by its skilful simplification of complex themes, and by its short and focused chapters – one being just 12 words long!

Overall assessment

With captivating story telling, excellent metaphors, great science, and human feeling, this book uniquely explores a subject which has significant application to almost all fields of medicine. By providing a comprehensive account of the subject, delving into its relevant history and exploring its exhilarating breakthroughs, the author has provided a balanced perspective of the immune system. It is a masterclass in the elegance of a functioning immune system, and in the human capacity to endure it when it malfunctions. The book is revealing and insightful, and I recommend it to all doctors.

Book details

Publisher, Place, Year:  William Morrow, New York, 2019
Number of chapters: 55
Number of pages: 425
ISBN: 978-0-06-269849-0
Star rating: 5
Price: £20.00

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