In 1974 a seminal paper drew attention to the very high rates of type 2 diabetes in many native populations of the Americas, Greenland, Polynesia, Micronesia and Melanesia (West 1974). West suggested that diabetes was probably uncommon in these groups prior to 1940, and noted that rates were still very low in those least touched by market economies. The high rates of diabetes in these populations were initially most often ascribed to a genetically based susceptibility to the development of obesity and associated diseases on the adoption of a western way of life. This explanation is commonly known as the ‘thrifty genotype’ hypothesis. An alternative explanation is that the susceptibility of these populations lies solely in the rapid changes of lifestyle they have experienced. Thus, it has been suggested that those born into a relatively poor environment may, if they later encounter a more western environment, be vulnerable to the development of obesity-related diseases. This latter explanation is sometimes referred to as the ‘thrifty phenotype’ hypothesis, to highlight its contrast with the thrifty genotype hypothesis. In this chapter I describe the populations best known for their very high rates of type 2 diabetes and cardiovascular disease, and then go on to consider in detail the competing explanations offered for these high rates of disease. I focus particularly on the debate about the causation of type 2 diabetes.

The inspiration for this book originates with Professor Geoffrey Ainsworth Harrison of the University of Oxford, who taught me and many others the value of the evolutionary approach to human biology. The third edition of the textbook he wrote with Paul Baker and others (Harrison et al. 1988) was a defining part of the curriculum at Oxford and I draw strongly on the approach of that volume in this book. He also introduced us to literature on western diseases published in the 1970s and 1980s by Boyden, and by Trowell and Burkitt, described at the beginning of Chapter 1. His supervision of my postgraduate work provided invaluable further opportunity to learn from his methods and ideas. In my subsequent career I have benefited greatly from this solid and stimulating foundation.

In my own teaching of advanced undergraduates and graduate students at Durham University I have felt the lack of an up-to-date equivalent of these texts, a feeling that was the main motivation for me to write this book. In the intervening years I have also benefited from exposure to epidemiological research on cardiovascular disease and other western diseases, and I hope that the end result profits from my learning beyond anthropology. My aim has been to draw these two approaches together to create a new synthesis. I am aware, of course, that in aiming for such a synthesis I have failed to provide the level of evolutionary theory that some evolutionary biologists and biological anthropologists would wish to see, while offering less detail of biomedical and epidemiological research than might be expected from the other side.

This book sets out to examine why certain non-communicable diseases have become common, first in affluent western populations and now, increasingly, worldwide. I use an evolutionary perspective because of its value in showing us why and how human bodies are vulnerable to these diseases. In this chapter I introduce the concept of western diseases and outline the evolutionary perspective applied throughout the book.

Western diseases

In the 1960s and 1970s concerns developed about the rise of diseases such as coronary heart disease, type 2 diabetes and colon and breast cancer as important causes of mortality and morbidity in the western world (Cleave et al. 1969; Boyden 1970; Burkitt 1973). The origins of the term western diseases, and of the approach I adopt in this book, lie in this work. The diseases identified were linked to ‘modern western civilisation’ and were considered to be ‘man-made’ (Trowell and Burkitt 1981a). Specifically, the rise of western diseases was blamed on increased availability of food (accompanied by a decline in the consumption of dietary fibre) and a reduction in physical activity. These authors also acknowledged the impact of an increase in life expectancy, which led to a higher proportion of susceptible older people in the population. The emergence of western diseases in non-western societies, for example in the Far East and in Africa, was linked to the process of westernisation, that is, the adoption of elements of the modern western lifestyle in other areas of the world (Trowell and Burkitt 1981b), a simplistic but nevertheless helpful concept.

Many researchers and lay members of society have expressed, or can identify with, the view that the modern western lifestyle does not nurture good mental health. The biggest foci of concern are depression and stress, both identified as increasingly important causes of ill health around the world, particularly in western societies.

According to biomedicine, depression can be an emotion, a symptom, or a disease. Lesser feelings of depression form part of the normal range of emotional experience, while clinical depression is classified as a psychiatric illness. Rates of diagnosed clinical depression have increased in the United States, Sweden, Germany, Canada and New Zealand since the Second World War and there appears to have been a decrease in the average age of onset of depression (Klerman and Weissman 1989). Projections suggest that depression is likely to be only second in importance to coronary heart disease as a cause of ill health worldwide by 2020 (Murray and Lopez 1997) and to maintain that position in 2030 (Mathers and Loncar 2006).

When people talk about being stressed, they usually mean that they are struggling to cope with the demands being made of them, and this is also the sense in which the term stress is now most often used by academics. There is a shared notion that people living in affluent industrialised societies live increasingly stressful lives, working long hours, undertaking long commutes, juggling the demands of work and family, struggling to find time for exercise, and suffering from ill health as a consequence, and that this kind of life generates more stress and stress-related disease than humans have ever felt before.

The rise of asthma and allergic diseases in most affluent countries of the world over the last 40 years has been striking, and many theories have been proposed to explain the phenomenon. These theories help us to understand what has gone wrong in our bodies when we have an allergic response to apparently harmless substances, such as cat dander, pollen or peanuts. Some of these ideas incorporate evolutionary insights, in particular, the suggestion that the human immune system is now lacking contact with organisms that would previously have had an important role in directing its development.

The scale of the problem

What is asthma?

The term asthma has usually been used to describe attacks of shortness of breath and wheezing caused by swollen and inflamed airways that are prone to constrict suddenly and violently. It is more commonly seen in children than in adults. However, there is increasing concern that the term is used to describe a range of conditions that do not necessarily share common underlying pathologies (Lancet Editorial 2006). There is no single biological marker or clinical test for asthma, and symptoms, triggers and responses to treatment are variable. The most common distinction is between allergic and non-allergic asthma, with allergic asthma being more common, particularly in children. But categorising a given case of asthma, even according to this broad dichotomy, can be difficult (Wenzel 2006).

Living in an affluent western society brings many advantages for health, notably security from hunger and from the serious infectious diseases of infancy and childhood that plagued western countries prior to the twentieth century and continue to inflict a heavy burden on populations in poorer countries today. However, as we have seen, westerners suffer from a characteristic set of relatively new non-communicable diseases, and these diseases are seen in non-western populations at increasingly high rates. In this concluding chapter I first summarise what an evolutionary perspective offers to the study of human vulnerability to western diseases. Next, I consider prospects for the future, focusing on what ‘westernisation’ means for the health of the millions of people subject to its influence, and on the insights that an evolutionary perspective provides in relation to possible preventive strategies.

Human vulnerability to western diseases

This book has shown that humans are vulnerable to western diseases because, as a species, we evolved in very different environments from those experienced today. We can summarise these effects in relation to obesity, in many respects the core pathology underlying western diseases. When the genus Homo emerged, selective pressures related especially to having a large brain led to these early hominins becoming proportionately fatter than other species of the tropical savannah. Humans also evolved under selective pressures imposed by the necessity of eating wild animals and plants and being physically active. The human genotype was ‘thrifty’, making effective use of scarce resources.

Obesity is common and increasing in prevalence in Europe, North America, Australia and Latin America, particularly among the young (Seidell 1995; Martorell et al. 1998; Midthjell et al. 1999; Catanese et al. 2001; Tremblay et al. 2002; Thorburn 2005). While obesity emerged first in western populations, it is rapidly spreading to poorer countries (Yoon et al. 2006). Considerable concern has been expressed in the medical literature, as well as more widely, about the obesity ‘epidemic’ and its associated health consequences. In this chapter I outline the evolutionary context for the emergence of obesity as a major health problem, comparing what we know about diet and energy expenditure, the main determinants of obesity levels, in hunter–gatherer societies and in industrialised countries today. I also examine the closely related diseases type 2 diabetes and cardiovascular disease. Some populations seem to be particularly vulnerable to the development of obesity and related diseases, an issue explored in Chapter 4.

Diet, physical activity and body composition in humans before agriculture

The first members of the taxonomic group to which apes and humans belong (hominoids) lived 30 million years ago and subsisted largely on fruit, with some vegetable foods and meat. Meat began to assume more importance in the hominin line from around 7 million years ago, particularly with the advent of stone tools about 2 million years ago (Richards 2002).

Microbes import the materials needed for growth and survival from their environment and export metabolites. As described in the previous chapter, the cytoplasm is separated from the environment by the hydrophobic cytoplasmic membrane, which is impermeable to hydrophilic solutes. Because of this permeability barrier exerted by the phospholipid component, almost all hydrophilic compounds can only pass through the membrane by means of integral membrane proteins. These are called carrier proteins, transporters or permeases (a website devoted entirely to transport can be found at www-biology.ucsd.edu/∼msaier/transport/).

Solute transport can be classified as diffusion, active transport or group translocation according to the mechanisms involved. Diffusion does not require energy; energy is invested for active transport; and solutes transported by group translocation are chemically modified during this process. Some solutes are accumulated in the cell against a concentration gradient of several orders of magnitude, and energy needs to be invested for such accumulation.

Ionophores: models of carrier proteins

There are two models which explain solute transport mediated by carrier proteins: the mobile carrier model and the pore model. The solute binds the carrier at one side of the membrane and dissociates at the other side according to the mobile carrier model, while the pore model proposes that the carrier protein forms a pore across the membrane through which the solute passes. A certain group of antibiotics can make the membrane permeable to ions. These are called ionophores and are useful compounds to assist the study of membrane transport.

It has been described previously how glucose and mineral salts can support the growth of certain heterotrophs. In this case, the organisms obtain ATP, NADPH and carbon skeletons for biosynthesis through central metabolism. Almost all natural organic compounds can be utilized through microbial metabolism. In this chapter, the bacterial metabolism of organic compounds other than glucose is discussed. Since central metabolism is reversible in one way or another, it can be assumed that an organism can use a compound if that compound is converted to intermediates of central metabolism. Some bacteria can use an extensive variety of organic compounds as sole carbon and energy sources, while some organisms can only use limited numbers of organic compounds; for example, Bacillus fastidiosus can use only urate.

Hydrolysis of polymers

Plant and animal cells consist mainly of polymers. They include polysaccharides, such as starch and cellulose, as well as proteins, nucleic acids, and many others. Such polymers cannot be easily transported into microbial cells but are first hydrolyzed to monomers or oligomers by extracellular enzymes before being transported into the cell.

Starch hydrolysis

Starch is a glucose polymer consisting of amylose and amylopectin. The former has a straight chain structure with α-1,4-glucoside bonds, while the latter has side chains with α-1,6-glucoside bonds. Starch is the commonest storage material in plants, and many prokaryotes produce amylase to utilize it as their energy and carbon source.

Like all organisms, microorganisms grow, metabolize and replicate utilizing materials available from the environment. Such materials include those chemical elements required for structural aspects of cellular composition and metabolic activities such as enzyme regulation and redox processes. To understand bacterial metabolism, it is therefore helpful to know the chemical composition of the cell and component structures. This chapter describes the elemental composition and structure of prokaryotic cells, and the kinds of nutrients needed for biosynthesis and energy-yielding metabolism.

Elemental composition

From over 100 natural elements, microbial cells generally only contain 12 in significant quantities. These are known as major elements, and are listed in Table 2.1 together with some of their major functions and predominant chemical forms used by microorganisms.

They include elements such as carbon (C), oxygen (O) and hydrogen (H) constituting organic compounds like carbohydrates. Nitrogen (N) is found in microbial cells in proteins, nucleic acids and coenzymes. Sulfur (S) is needed for S-containing amino acids such as methionine and cysteine and for various coenzymes. Phosphorus (P) is present in nucleic acids, phospholipids, teichoic acid and nucleotides including NAD(P) and ATP. Potassium is the major inorganic cation (K+), while chloride (Cl−) is the major inorganic anion. K+ is required as a cofactor for certain enzymes, e.g. pyruvate kinase. Chloride is involved in the energy conservation process operated by halophilic archaea (Section 11.6). Sodium (Na+) participates in several transport and energy transduction processes, and plays a crucial role in microbial growth under alkaline conditions (Section 5.7.4).

Escherichia coli can grow on a simple medium containing glucose and mineral salts and this bacterium can synthesize all cell constituents using materials provided in this medium. Glucose is metabolized through the Embden–Meyerhof–Parnas (EMP) pathway and hexose monophosphate (HMP) pathway and the metabolic product, pyruvate, is decarboxylated oxidatively to acetyl-CoA to be oxidized through the tricarboxylic acid (TCA) cycle. Twelve intermediates of these pathways are used as carbon skeletons for biosynthesis (Table 4.1). Heterotrophs that utilize organic compounds other than carbohydrates convert their substrates into one or more of these intermediates. For this reason, glucose metabolism through glycolysis and the TCA cycle is called central metabolism.

Eukaryotes metabolize glucose through the EMP pathway to generate ATP, pyruvate and NADH, and the HMP pathway is needed to supply the metabolic intermediates not available from the EMP pathway such as pentose-5-phosphate and erythrose-4-phosphate, and NADPH. Most prokaryotes employ similar mechanisms, but some prokaryotes metabolize glucose through unique pathways known only in prokaryotes, e.g. the Entner–Doudoroff (ED) pathway and phosphoketolase (PK) pathway. Some prokaryotes have genes for the ED pathway in addition to the EMP pathway: genes for these pathways are expressed at the same time in several prokaryotes including a thermophilic bacterium (Thermotoga maritima), a thermophilic archaeon (Thermoproteus tenax) and a halophilic archaeon (Halococcus saccharolyticus). Escherichia coli metabolizes glucose via the EMP pathway, but gluconate is oxidized through the ED pathway. Modified EMP and ED pathways are quite common in archaea.

As mentioned repeatedly in this book, the goal of life is preservation of the species through reproduction, but this requires energy. Although there are a few exceptional copiotrophic environments such as foodstuffs and animal guts, most ecosystems where microorganisms are found are oligotrophic. Those organisms that can utilize nutrients efficiently have a better chance of survival in such ecosystems. Further, many microbes synthesize reserve materials, when available nutrients are in excess, and utilize these under starvation conditions, while various resting cells are produced under conditions where growth is difficult. In this chapter, the main bacterial survival mechanisms are discussed in terms of reserve materials and resting cell types.

Survival and energy

As discussed earlier, living microorganisms maintain a certain level of adenylate energy charge (EC) and proton motive force even under starvation conditions (Section 5.6.2). These forms of biological energy are needed for the basic metabolic processes necessary to survive such as transport and the turnover of macromolecules. Maintenance energy is the term used for this energy.

Under starvation conditions, cells utilize cellular components including reserve and non-essential materials for survival. This is referred to as endogenous metabolism. Almost all prokaryotes accumulate at least one type of reserve material under energy-rich conditions. During a period of starvation, the reserve material(s) are consumed through endogenous metabolism before the organism oxidizes other cellular constituents such as proteins and RNA that are not needed under the starvation conditions (Figure 13.1).

In the previous chapter, respiration was defined as an energy conservation process achieved through electron transport phosphorylation (ETP) using externally supplied electron acceptors. Electron acceptors used in anaerobic respiration include oxidized sulfur and nitrogen compounds, metal ions, organic halogens and carbon dioxide. Other oxidized compounds reduced under anaerobic conditions include iodate, (per)chlorate, and phosphate. There is evidence to suggest that these compounds are used as electron acceptors in anaerobic ecosystems but there are some exceptions. ATP synthesis mechanisms dependent on a proton motive force are known in some fermentative bacteria. These include Na+-dependent decarboxylation, fumarate reduction and product/proton symport, as described earlier (Section 5.8.6). Sulfidogenesis and methanogenesis are described as fermentations in some cases since a small amount of energy is conserved in these anaerobic processes. However, in these processes ATP is generated mainly through the proton motive force and they can therefore be classified as anaerobic respiration.

Many ecosystems become anaerobic when oxygen consumption is greater than its supply. Even under anaerobic conditions, natural organic compounds are continuously recycled. Anaerobic respiratory microbes convert organic materials to carbon dioxide and methane under anaerobic conditions in conjunction with fermentative microbes.

Energy is required for all forms of life. At any given conditions, those organisms utilizing energy sources more efficiently will become dominant over the others. Among the anaerobic respiratory prokaryotes, denitrifiers conserve more energy than other groups. For this reason sulfidogenesis and methanogenesis are inhibited in the presence of nitrate, and sulfate inhibits methanogenesis.

Life processes transform materials available from the environment into cell components. Organic materials are converted to carbon skeletons for monomer and polymer synthesis, as well as being used to supply energy. Microbes synthesize monomers in the proportions needed for growth. This is possible through the regulation of the reactions of anabolism and catabolism. With a few exceptions, microbial ecosystems are oligotrophic with a limited availability of nutrients, the raw materials used for biosynthesis. Furthermore, nutrients are not usually found in balanced concentrations while the organisms have to compete with each other for available nutrients.

Unlike animals and plants, unicellular microbial cells are more directly coupled to their environment, which changes continuously. Many of these changes are stressful so organisms have evolved to cope with this situation. They regulate their metabolism to adapt to the ever-changing environment.

Since almost all biological reactions are catalyzed by enzymes, metabolism is regulated by controlling the synthesis of enzymes and their activity (Table 12.1). Metabolic regulation through the dynamic interactions between DNA or RNA and the regulatory apparatus employed determine major characteristics of organisms. In this chapter, different mechanisms of metabolic regulation are discussed in terms of enzyme synthesis through transcription and translation and enzyme activity modulation.

Mechanisms regulating enzyme synthesis

The rate of biological reactions catalyzed by enzymes is determined by the concentration and activity of the enzymes. Various mechanisms regulating the synthesis of individual enzymes are discussed here before multigene regulation is considered.

Knowledge of the physiology and metabolism of prokaryotes underpins our understanding of the roles and activities of these organisms in the environment, including pathogenic and symbiotic relationships, as well as their exploitation in biotechnology. Prokaryotic organisms include bacteria and archaea and, although remaining relatively small and simple in structure throughout their evolutionary history, exhibit incredible diversity regarding their metabolism and physiology. Such metabolic diversity is reflective of the wide range of habitats where prokaryotes can thrive and in many cases dominate the biota, and is a distinguishing contrast with eukaryotes that exhibit a more restricted metabolic versatility. Thus, prokaryotes can be found almost everywhere under a wide range of physical and chemical conditions, including aerobic to anaerobic, light and dark, low to high pressure, low to high salt concentrations, extremes of acidity and alkalinity, and extremes of nutrient availability. Some physiologies, e.g. lithotrophy and nitrogen fixation, are only found in certain groups of prokaryotes, while the use of inorganic compounds, such as nitrate and sulfate, as electron acceptors in respiration is another prokaryotic ability. The explosion of knowledge resulting from the development and application of molecular biology to microbial systems has perhaps led to a reduced emphasis on their physiology and biochemistry, yet paradoxically has enabled further detailed analysis and understanding of metabolic processes. Almost in a reflection of the bacterial growth pattern, the number of scientific papers has grown at an exponential rate, while the number of prokaryotic genome sequences determined is also increasing rapidly.

Anaerobic conditions are maintained in some ecosystems where the rate of oxygen supply is lower than that of consumption. Organic compounds are removed from anaerobic ecosystems through the concerted action of fermentative and anaerobic respiratory microorganisms. In microbiology, the term ‘fermentation’ can be used to describe either microbial processes that produce useful products or a form of anaerobic microbial growth using internally supplied electron acceptors and generating ATP mainly through substrate-level phosphorylation (SLP).

Electron acceptors used in anaerobic metabolism

Fermentation and anaerobic respiration

Respiration refers to the reduction of oxygen by electrons from the electron transport chains coupled to the generation of a proton motive force through electron transport phosphorylation (ETP; Section 5.8). Under anaerobic conditions, some microorganisms grow using an ETP process with externally supplied oxidized compounds other than oxygen as the terminal electron acceptor. This type of growth is referred to as anaerobic respiration. In a fermentative process, ATP is generated through SLP with the oxidation of electron donors coupled to the reduction of electron carriers such as NAD(P)+ or flavin adenine dinucleotide (FAD). The reduced electron carriers are reoxidized reducing the metabolic intermediate.

This chapter describes the fermentation processes carried out by various anaerobic prokaryotes. In fermentation, ATP is generated not only through SLP but also by other mechanisms such as the reactions catalyzed by fumarate reductase and Na+-dependent decarboxylase, and lactate/H+ symport as described earlier (Section 5.8.6).

Chapters 4 and 5 describe and explain the anabolic reactions that supply carbon skeletons, reducing equivalent (NADPH) and adenosine 5′-triphosphate (ATP) needed for biosynthesis. This chapter summarizes how the products of such anabolic reactions are used in biosynthesis and growth, ranging from monomer synthesis to the assembly of macromolecules within cells. Chemoheterotrophs, such as Escherichia coli, use approximately half of the glucose consumed to synthesize cell materials while the other half is oxidized to carbon dioxide under aerobic conditions.

Molecular composition of bacterial cells

The elemental composition of microbial cells was discussed in Chapter 2 in order to help understand what materials the bacteria use as their nutrients. These elements make up a range of molecules with various functions. Cellular molecular composition varies depending on the strain and growth conditions. As an example, Table 6.1 lists the molecular composition of Escherichia coli during the logarithmic phase when grown on a glucose–mineral salts medium. The moisture content is over 70%, and protein is most abundant, occupying 55% of the dry cell weight, followed by RNA at about 20%. It is understandable that proteins are abundant since they catalyze cellular reactions. The DNA content is least variable, while the RNA content is higher at a higher growth rate. Not shown in Table 6.1 are storage materials, such as poly-β-hydroxybutyrate and glycogen, which vary profoundly within cells depending on growth conditions, and can comprise up to 70% of the cell dry weight (Section 13.2).