The Evolution & Medicine Review

A constructively critical appraisal of the hygiene hypothesis in evolutionary perspective

Book Review: The Hygiene Hypothesis and Darwinian Medicine

Graham A.W. Rook, Editor

Progress in Inflammation Research, Michael J. Parnham, Series Editor

Birkhäuser Verlag AG, Basel, Boston, Bern

ISBN 978-3-7643-8902-4

The hygiene hypothesis (David Strachan, Brit Med J 299:1259-1260, 1989) has done much to literally bring immunology into household conversations, in a meaningful and practical way. How should we balance the risk of acutely dangerous infections in our babies and toddlers with a supposedly healthy exposure to environmental microbes and non-infectious agents to limit the lifetime risk of asthma and autoimmune disease? As a light-toned example, in some Western countries, the slightly neurotic midnight sterilization of baby feeding bottles and boiled water has only very recently given way to the much more relaxed use of hot tap water.

However, from a scientific perspective the original hygiene hypothesis posed serious problems from the onset, as borne out by sharply contrasting studies and emphasized by overly optimistic interpretation at points. Obviously, the obstacles for human epidemiological studies to correlate early age exposure to disease later in life are huge and difficult to overcome. Conversely, experimental data using inbred mouse strains in ultra-clean animal facilities can easily be questioned in terms of relevance for the human situation. Nevertheless, the hygiene hypothesis has been a fruitful paradigm to drive and direct research, and it has productively  “morphed” by the accruing evidence.

Dr. Graham Rook from University College London has taken on the laudable task to explore this reworking of the hygiene hypothesis as it stands mid-2009, and to do so from an evolutionary medicine perspective. He recruited 24 experts from different fields to write 15 concise and insightful chapters in 300 pages.

To leave no doubt, this  book is well worth reading.

It provides a highly welcome overview of the hypothesis from different angles, with an understandable immunology emphasis. These include anthropological expertise on epidemiology (George Armelagos), the evidence for relations between infection and childhood leukemia (Mel Greaves), and for the less often discussed implications of the hypothesis for atherosclerosis (Hafid Ait-Oufella and colleagues), psychiatric disorders (Graham Rook and Christopher Lowry), and for Alzheimer disease (Sue Griffin and Robert Mrak). Some authors are actively developing novel therapies to treat bowel inflammation with parasites and their products (David Elliott and Joel Weinstock).

Importantly, the book also addresses limitations to the hygiene hypothesis, as well as alternative and additional mechanisms (Margo Honeyman and Leonard Harrison). Refreshingly, some authors sound clearcut critical notes: for instance, much better definition of the underlying mechanisms are needed for allergy-protective interventions by infection: “Until then, any further attempts to prevent allergies with products lacking a solid rationale have to be regarded as doubtful, empiric and perhaps non-ethical enterprises” (Paolo Matricardi and Eckard Hamelmann).

Throughout the book, Rook’s own notion of Old Friends is discussed, the gut microbiota and environmental saprophytes with whom humans developed dependence through evolution. This is done in a balanced way and the Editor himself states clearly “It is not the purpose of this book to suggest that all of the increase in chronic inflammatory disorders is due to diminished contact with the old friends”.

Does the book leave anything to wish for? Of course it does, but much of that has to do with the truly staggering increase in pace with which the immunology field is developing, and the time it takes to bring a book to print and to the readers desk. For instance, other than the Toll-like receptors (TLR) recognizing both microbial and self molecules, and the NOD receptors responding to bacterial peptidoglycan fragments, the book does not devote much attention to other members the NLR family of innate antigen receptors. The same holds true for the RIG-I like helicases (RLH family), responding to both viral RNA and self DNA when accessing the cytoplasm. The novelty of the recent studies is underscored by a special issue of Science January 15th 2010 focusing on these families in innate immunity. As another example, exciting experimental work on relations between gut flora and obesity was too recent to include in the book.

An item that could have been addressed more in depth, and early on in the book, is the true and primary evidence on worldwide trends in asthma, other allergic afflictions, and the wide spectrum of autoimmune diseases. The book has a scattered 6 graphs on these trends, but only the rise in inflammatory bowel diseases (IBD: Crohn’s and ulcerative colitis) is discussed in depth. Why are these numbers so important? The emphasis in the hygiene hypothesis has always been on allergy, asthma, and on only a selection of inflammatory/autoimmune diseases, mostly type 1 diabetes, IBD and multiple sclerosis. I would argue that much can be learned from a systematic listing of prevalence trends in the spectrum of autoimmune diseases ranging from highly systemic to mostly organ-restricted. Also the female-male ratios within this spectrum, and changes in this ratio – supposedly increasing in multiple sclerosis – is potentially informative. And echoing Mel Greaves’ discussion of population mixing as a factor in acute lymphoblastic leukemia, to what extent have these prevalence numbers been analysed in terms of migration and subsequent alterations in national populations?

Finally, how strong is the evolutionary medicine component of the book? It is well-covered looking back over evolution anthropologically and immunologically. Conversely, how Darwinian theory will stimulate progress in hygiene hypothesis research could have been more strongly developed.

Notwithstanding these remarks, in conclusion, this book is a highly worthwile addition to existing literature. In view of its broadness and depth, and its critical appraisal of the hygiene hypothesis. It is useful for teaching purposes as well as for researchers from different fields, and the chances are good that it will  gain soundbite notoriety as The Rook Book.

Prof.Dr. Jon D. Laman

Department of Immunology, Ee 800

Erasmus MC, University Medical Center Rotterdam

This Supplement includes 18 open access papers from an April, 2009  Sackler Colloquium at the National Academy of Sciences: Evolution in Health and Medicine Sackler Colloquium

Citation: Evolution in Health and Medicine, PNAS, Vol 107 (suppl 1), 1691-1808, 2010. Continue Reading »

Press Release from National Evolutionary Synthesis Center, Contact: Robin Ann Smith rsmith@nescent.org

A Special issue of PNAS explores how evolution can help doctors understand and treat disease

		IMAGE: Evolutionary theory can help us tackle diverse problems in medicine and public health, says a growing body of researchers and physicians. Click here for more information.

Durham, NC – What does evolution – a field that often deals with changes over many generations – have to do with preventing and treating disease in our lifetime? A lot, some scientists say. If recent recommendations are implemented, future physicians may soon be tested on evolution in medical entrance and licensing exams, says an international group of doctors and researchers.

A collection of articles in the January 26 issue of Proceedings of the National Academy of Sciences illustrates recent progress in applying evolutionary theory to a range of questions in medicine and public health, from why some people age slower and live longer than others, to why humans suffer from mental illnesses like autism and schizophrenia, to why we have higher rates of cancer than other species.

“There are many ways you can use evolution to improve medical care and medical research,” said psychiatrist Randolph Nesse of the University of Michigan. Continue Reading »

According to an article, in 2005, by Nicholas Wade of The New York Times, the notion that human evolution had effectively stalled in the distant past (i.e., 50,000 years ago) had been widely accepted.  As recently as 2007, the eminent Harvard psychologist, author, and advocate for evolution, Steven Pinker, revealed, in the context of announcing a change in his views, that he had believed for many years that human evolution had ceased some thousands of years earlier by the time of the agricultural revolution.  Although I have previously argued (2008) that neither first principles nor the totality of available evidence (even some years back) offer much support for this concept of human evolution having ground to a halt, there have been significant challenges in devising reliable methods by which DNA sequence information alone could be used to infer the action of selection on particular genes or regions of the genome.

A new study from Grossman et al., published online in Sciencexpress, reports a novel approach to identifying causal genetic variants responsible for positive selection in human (and possibly other) genomes.  Actually, Sabeti and colleagues describe a fusion of three pre-existing methods as well as two new techniques for identifying such genetic variants.  Continue Reading »

Tags: derived alleles, differentiated alleles, haplotype length, positive selection

Read the Full Text (No open access)

This post compiles reports from the five Workshops at the Meeting Evolution and Diseases of Modern Environments, at the Berlin Charite Hospital, October, 2009.  The workshops were held in conjunction with The World Health Summit.

Diet and Nutrition Workshop Report

Early Development and Reproductive Health Workshop Report

Evolution and Mental Disorders Workshop Report

Sanitizing the Hygiene Hypothesis Workshop Report

Developmental Aspects Of Diseases Of Modern Environments Workshop Report

Quirks of Human Anatomy by Lewis Held, Cambridge University Press, 2009.

Book Review

Held Book Cover

The emergence of Darwinian (evolutionary) medicine had led to a renaissance of many long forgotten biological topics, among which are atavistic traits (traits of our ancestors). These traits that disappeared long ago from our lineage are occasionally reappearing in present human populations, allowing a glance to our remote biological history. This is possible because the genes behind these traits are still preserved in our DNA, although not expressed in most individuals. Atavistic traits together with vestigial structures (structures that lost all or most of their original function in a species through evolution) played a major role in the establishment of Darwinian Theory prior to the emergence of modern genetics. The book Quirks of Human Anatomy revives many of these old ideas and questions (e.g., Where did our tail go?) and poses several new intriguing ones (e.g., Continue Reading »

Circulation. 2009;119:459-467
doi: 10.1161/CIRCULATIONAHA.108.809970

Keyue Ding, PhD; Iftikhar J. Kullo, MD

Nothing in biology makes sense except in the light of evolution.¹— —Theodosius Dobzhanksy, 1973

No biological problem is solved until both the proximate and the evolutionary causation has been elucidated. Furthermore, the study of evolutionary causes is as legitimate a part of biology as is the study of the usually physico-chemical proximate causes.²— —Ernst W. Mayr, 1982

Susceptibility to common diseases such as coronary heart disease (CHD) may in part reflect historical or evolutionary legacies,^3,4 and interest in studying evolutionary biology to gain novel insights into human health and disease is increasing. The evolutionary history of the human species may provide valuable insights into the origin of common diseases beyond what is possible by investigating only the most immediate or “proximal” causes of disease. The potential role of evolutionary biology in explaining disease causation was highlighted by Williams and Nesse³ and is often referred to as darwinian medicine. Although the relevance of an evolutionary perspective may vary depending on the disease under study, a strong argument could be made for studying the evolutionary genetics of CHD, a leading cause of human morbidity and death.

Within the last decade, several important advances have made it possible to study “modern” diseases from an evolutionary perspective. The Human Genome Project⁵ provided a reference human genome, and the subsequent International HapMap Project^6,7 described genetic variations (mostly single nucleotide polymorphisms [SNPs]) among individuals and the patterns of variation across the genome. Both projects provide the raw material to study natural selection in the . . . [Full Text of this Article]

According to both academic lore and history  (Paulos, 1985; Ryerson, 2004), the late Sidney Morgenbesser, a professor of philosophy at Columbia and a renowned conversationalist and wit, was once listening to an Oxford colleague, J. L. Austin, lecturing on the philosophy of language.  The eminent Professor Austin proceeded to claim that while a double negative can be taken as a positive, a double positive is never interpreted as a negative.  Morgenbesser responded with as concise and incisive a rebuttal as one might ever hope to unleash,”Yeah, yeah,” thereby decisively demonstrating the extent to which the meaning of words can be shaped by the linguistic environment in which they are embedded.

Last month, a report in Nature (Netzer et al.) described one mechanism that causes even the genetic code to be read in a somewhat context-dependent manner. Continue Reading »

Tags: infection, misacylation, oxidative stress, protein translation, Toll-like receptors (TLR), tRNA synthetases genetic code

What are the consequences of the disappearing human microbiota?
by Martin J. Blaser and Stanley Falkow
in Nature Reviews Microbiology   doi:10.1038/nrmicro2245

Who are we? From prions and organelles up through neighborhoods and nation-states, we are groups of groups of groups. In this thoughtful, provocative paper Blaser and Falkow remind us that 90% of our cells are non-human. Vertebrates coevolved with vast communities of microorganisms with whom they share complex endosymbiotic relationships. The authors assert that the human microbiome has been dramatically altered by changes in human ecology. They expand on their disappearing microbiota hypothesis, using the decreasing prevalence of Helicobacter pylori as an example, and argue that such alterations have physiologic and clinical consequences that must be better understood.

Mark D. Schwartz, MD
Associate Professor of Medicine
NYU School of Medicine

Abstract:
Humans and our ancestors have evolved since the most ancient times with a commensal microbiota. The conservation of indicator species in a niche-specific manner across all of the studied human population groups suggests that the microbiota confer conserved benefits on humans. Nevertheless, certain of these organisms have pathogenic properties and, through medical practices and lifestyle changes, their prevalence in human populations is changing, often to an extreme degree. In this Essay, we propose that the disappearance of these ancestral indigenous organisms, which are intimately involved in human physiology, is not entirely beneficial and has consequences that might include post-modern conditions such as obesity and asthma.