introduction

Professor Wieland Gevers of Medical Biochemistry and Deputy Vice-Chancellor of the University of Cape Town

Certain precepts absorbed by every student remain alive because they are continuously reinforced and underpinned during later intellectual growth and from practical experience.

For me, the carefully crafted 'generalised life history' model developed by Professor John F Brock, explained and elaborated to successive cohorts of medical students at the University of Cape Town in the 1950s and 1960s, has been a potent vehicle for the incorporation of much research-driven progress in medical knowledge since then. The interaction of 'Nature' (seen as a changing rather than a static, comprehensive genotype, from conception to birth to maturity to senescence) with 'Nurture' (the sporadic or repeated slings and arrows of nutritional, infective or accidental bad fortune) give each individual, encountered by a health-care professional at any particular time, a unique current 'working mechanism': failure to understand this background concept dramatically impairs the care-giver's ability both to diagnose presenting disorder and to treat it effectively.

The spectacular advances in medical genetics have begun wonderfully to give flesh to those parts of Brock's model that were shrouded in phenomenological mystery two decades ago. The existence of batteries of tumour-suppressor genes (inherited or acquired mutations of which permit cancerous cellular growth if other conditions are met), of oncogenes (altered expression or mutation-caused function of which can cause various types of usually sequential cancerous cellular behaviours, from over-growing' to 'failing to die' to 'invading surrounding tissues' to 'metastasising'), now allows us mechanistically to explain the formation of benign or malignant tumours in particular tissues, in particular sites, at particular ages, in particular people. We can explain it, provided (and this remains very important) that external factors (carcinogens) are not forgotten as by far the most frequent root causes of altered structure and/or function of these very important, inter-acting genes.

Thus, one person can smoke heavily for 70-80 years and die of 'old age', while another will die of bronchial carcinoma at age 55 after smoking for only 30 years. The second type of person is unfortunately, but significantly, much more common than the first, but we are beginning to be able to understand why we will encounter both individuals in any reasonably large population.

There are many other well-understood examples of interactions between different genes or between certain inherited deleterious genes and the environment. Persons who are heterozygous for low­-density lipoprotein receptor gene mutations and who therefore suffer from a form of familial hypercholesterolaemia which is much less severe than do those who are homozygous for the same defects, die from accelerated atherosclerosis on average a decade earlier if they also have high levels of the product of a second, unrelated gene, that for Lipoprotein (a). Individuals who have genetically caused alpha-antitrypsin deficiency develop severe emphysema at a much earlier stage, if they smoke, than do individuals without this deficiency.

Age-dependent phenotypic disease expression is a feature of many conditions caused by dominantly acting deleterious genes, e.g. Huntington's Chorea. While we still do not understand why three or four decades of apparently normal brain function are almost invariably followed in this condition by rapidly progressing dysfunction and death, we know of fascinating examples of programmed changes in the expression of certain genes during life (e.g. the lactase gene in the intestines which in most humans 'shuts down' after weaning), and there are likely to be many such changes during middle-life and certainly in senescence.

Another important concept which has a bearing on 'Nature-Nurture' is the considerable redundancy or spare capacity with which our important systems have been endowed by evolution. For example, many persons seem to function quite normally even though they are taking beta-blocking drugs at doses that effectively eliminate processes, which would otherwise quite reasonably be thought to be necessary for life, let alone for apparently normal functioning. Studies on experimental animals in which particular genes have been deliberately 'knocked-out' have shown a surprising resistance of the superbly integrated physiological systems to the expected lethal effects.

Put in simpler language, we clearly have redundant capacity (reserves) or compensatory mechanisms that are extremely effective in 'smoothing out' the effects of external agents or insults: we can 'take a lot of beating' over short or long periods, and this appears to be especially true for young individuals.

At the genetic level, the most universally important redundancy is the non-haploid state of the genome in living tissues: unless they act dominantly, gene mutations will be silent whether they are inherited or newly acquired. This 'protection' is worth a great deal and explains why age, and recurrent exposure to agents that enhance the rate of genetic damage, is so important a factor in the 'generalised life history' model of human health and disease.

This Technical Report is about chronic diseases of lifestyle and their importance in South Africa. The term 'chronic diseases of lifestyle' is shorthand for a group of diseases that have similar risk factors as a result of exposure, usually over many decades, to diets of a particular kind (high in kilojoules and saturated fats, low in dietary fibre), cigarette smoking, physical inactivity and psychological stress. This 'lifestyle complex' is obviously only one of many that are found in the modern world with its north-south polarisation, its many cultures and diverse climatic regions. The isolation of this lifestyle complex for special study and characterisation in South Africa is justified because of its preponderance among middle- and upper-income people, and because of its idealisation by most poor people.

Following a particular lifestyle over long periods produces a physiological adaptation, a particular 'Nurture', which, as discussed earlier. will interact progressively and cumulatively with the proceeding genetic 'programme' of each individual. One of the most significant, as yet only dimly understood, aspects of this situation in a multi-cultural country, stratified in terms of socioeconomic status, is that certain group genotypes may have evolved over centuries in regional environments which selected genetically for the capacity to cope, for example, with food scarcity or staple monotony. One hundred years after having been characterised as a healthy, lean population, the inhabitants of the island Nauru in the Pacific Ocean have turned their phosphate mine-derived wealth into a 50% incidence of diabetes and almost universal adult obesity. Something of this kind, even though less striking, may also have happened recently to the Indian population of Kwazulu-Natal, who now have the highest ischaemic heart disease rate of all South Africans.

The World Health Organisation has shown that chronic diseases become the major causes of death when any population's life-expectancy exceeds 60 years. furthermore the chronic diseases then occur in all strata of society of low socioeconomic standing in developed countries. Different chronic diseases affect everybody, and the more hopeful the vision we have of our 'rain bow-nation' future, the more important the proper management of this 'lifestyle complex' and its associated disorders will become.

The most fascinating feature of the chronic diseases of lifestyle is the question of personal choice. Well-off people can choose the food they eat (it is vastly cheaper to eat adequate but not excessive amounts of a prudent diet high in fibre-containing, starchy foods and low in saturated fats, than it is to eat excessive amounts of processed or refined foods rich in saturated fats), they can refrain from smoking, they can take regular vigorous exercise and they can try to avoid excessive psychological stress. The 'lifestyle devil' is the apparently irresistible temptation not to make such choices once one has money in one's pocket and/or the bank, and is covered by a commercial 'blanket' of conspicuous consumption and the glorification of risk-taking behaviours. The latter appear to be particularly satisfying because they are usually the easier options in any case: the grim reaper is most readily defied when your overweight body is deeply embedded in an easy chair, a lighted cigarette in one hand and a half-empty beer can in the other! This is a caricature, but the reality of a vast amount of avoidable ill-health, disability and premature mortality is predicated on the tension between the free choices that people individually exercise in a democratic society, and the cost to that society of providing health-care for those whose problems have been pulled down upon their own heads, so to speak.

This brings one to another aspect of the chronic diseases associated with the 'lifestyle complex' dealt with exhaustively in this Report. Societies where this lifestyle is predominant have pushed their average life expectancies up to near the limits apparently imposed by our natural mortality. Even in a society which universally accepts the most prudent lifestyles imaginable according to our present knowledge, there would be a 'mayhem' period of subacute or chronic degenerative disease in people between the ages of 75 and 95 years. Our concern with the chronic diseases of lifestyle in South Africa has to do with costly and debilitating morbidity long before this unavoidable twilight zone is reached and, for many, death long before the appointed time as a result of heart attack, stroke or cancer. In fact, these premature deaths and the preceding morbidity suffered by these patients have a major impact on the economy of South Africa: it is shown in Chapter 1 by Bradshaw et al that about 40% of people in the economically active age group (25-64 years) die because of these chronic diseases. It is this premature burden of disease that we must lighten, and the lifelong expectation of health, vigour and fitness that we must help to provide for every citizen.

It is likely that efforts to ameliorate the occurrence and severity of the chronic diseases of lifestyle (in this specific case, the 'lifestyle complex' associated with the 'good life') will be as important a factor in promoting good health in an affordable way, as will be the more obvious and socially immediate problem of combating malnutrition, infectious disease and trauma in people who are poor and underprivileged. Large parts of the population are, or will be, affected by the chronic diseases of lifestyle discussed in this Report - it is a very important matter for all of us.

This Technical Report has its origins in the recent re-appraisal by the MRC of its role in building a healthy nation through research. A Programme for Chronic Diseases of Lifestyle was established by the MRC early in 1995, building on the insights gained from the drafting of this Technical Report. It is important that the Reconstruction and Development Programme of the Government of National Unity explicitly includes the question of combating chronic diseases in its broad agenda. In the emerging democracy, the complex problem of 'imprudent lifestyles' will be a severe test of the ability of health authorities, researchers and the community at large to make choices that bring sustainable health and happiness rather than the inexorable penalties of self-destructive behaviours.

The authors of the chapters in this Report are all well-recognised and experienced experts in their different areas of work. Their contributions have been tightly edited by Dr Krisela Steyn, Programme Leader of the MRC's Chronic Diseases of Lifestyle Programme, and author of the policy proposals contained in the last chapter. She has worked tirelessly to bring this Report to completion, and our sincere thanks (speaking for all readers) are due to her and her select group of authors for this timely and important document, which allows us to identify and understand the enemy in our midst, chronic diseases of lifestyle.