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With the publication of the sequence of the human genome, we can now approach our history as human beings in a way never previously possible—a history that has been written in only 30000 or so genes. There is a completely different way of looking at history and genetics, however—one that should never be forgotten by clinicians.
Take a real case history: a 27 year old woman presents for a routine examination with a small lump on her breast. She had been seen by doctors who ignored the lump and took neither a biopsy nor an adequate history. The latest doctor to see her asked whether members of her family had had breast cancer. Both her mother and maternal grandmother died before the age of 40 from breast cancer. Whether their malignancies were caused by mutations in BRCA1 or 2, the p53, or other genes is unimportant: an adequate history would have revealed a great deal about her genetic susceptibility to disease. Classic papers,1,2 largely but not entirely forgotten,3 point out that 70% of diagnoses can be revealed in clinical histories, with laboratory diagnosis accounting for only about 10% additional information. For clinicians in developing countries, without access to advanced diagnostic facilities but with knowledge of genetic research, a careful history can reveal much of what modern genetics and high technology can teach that is important to general clinical practice.
What then is the relevance to developing countries of the scientific advance represented by the mapping of the human genome? The first essential point is that its impact will vary. There are enormous differences between developing countries in burden of disease, financial resources, educational attainment, and health systems.4 Over the past decade five African countries have seen a decline in life expectancy to below 40 years, while others have seen it grow. Some countries lose one child in five to infectious diseases and others, such as Botswana, two in five of their young people to AIDS. Others, including India, Brazil, Indonesia, and Korea, have biotechnology industries capable of producing new and high quality, low cost generic drugs.5 Vietnam, South Africa, China, and Brazil are endeavouring to develop their own essential vaccines, although they are doing so in the face of competition from multinationals. Of concern is the fact that new drugs and vaccines are being developed to export for profit rather than to sell cheaply to local people.6
The human genome undoubtedly offers unprecedented opportunities to all countries for understanding mechanisms of disease and developing new drugs and vaccines. All the drugs in the world act on only 479 known molecular targets. If only 10% of the genome represents targets for new drugs the possibility exists for developing at least 3000 new molecular entities to combat disease. Through new technologies 50000 new drugs can be produced and screened by a laboratory in a week—more than a major pharmaceutical company could test in a year.
Already new vaccines are under development that have been derived directly from the DNA sequence of the pathogen. The most advanced is a vaccine for meningococcal meningitis, currently being assessed in phase I clinical trials in Italy. If it can be done for meningococcal infection it can also be done for other infectious diseases where the DNA sequence of the pathogens is known. Whether and how fast new vaccines will be developed will depend on rich countries, and those with means in poor countries, recognising that global health is a priority that transcends national boundaries and committing resources for such research.
For rich countries genetic advances are fuelling the development of sophisticated DNA chips. These may be used to identify tiny differences between individuals' genes that predict genetic risks for disease in infancy for which preventive measures and lifestyle changes could, in principle, be adopted. Such tests may create “boutique medicine,” drugs targeted to overcome the special risks of individuals. Rich kids may end up taking lots of pills to avoid genetically predisposing risks without having to change their lifestyle.
Yet even when genetic information is available it is important to recognise that genes are not destiny. The outcome of most diseases depends on multiple and complex interactions between genes and environment. Even when the genetics of common disease is unravelled and genetic risks are identified, most people are unlikely to change their behaviour and avoid major health risks such as smoking. There is also a lesson in humility to be learnt from the human genome project. We are unlikely to learn more about any disease than we already know about sickle cell disease. We know the gene and its mutations, the protein and its structure, and the mechanism of loss of function, yet we can still do little for patients.
The information that can be gleaned from the human genome project must be shared with developing countries. Better diagnostic algorithms and probing questionnaires, hopefully informed by genome information, should improve the identification of patients suffering from genetic diseases, particularly common disorders such as sickle cell disease, thalassaemias, and cystic fibrosis. New technology should provide simpler diagnostics such as dipsticks, although this will probably depend on whether there are markets for these in rich countries. Nevertheless, the diagnostic tools the rich world takes for granted, such as chorionic villus sampling for antenatal diagnosis and simple electrophoresis for detecting abnormal haemoglobin, are out of the reach of the poorest countries. And even if they were available, antenatal counselling and the opportunity to terminate affected pregnancies safely may not be.
So what can be offered to poor countries? The genome project is not a substitute for disease prevention or changing risk behaviours, but the World Bank has estimated that in some cases (for example, cholera) it is more cost effective, from the point of view solely of protecting human health, to treat patients than to invest huge sums in cleaning up air, water, or environmental pollution.7 Our hope is that knowledge of the genome will encourage some medical researchers to seek new interventions that are population based and that emphasis will be put on developing inexpensive drugs (comparable to aspirin and β blockers) and vaccines that prevent disease and disability in populations, rather than individual based designer therapies. If not, the human genome project has the potential to widen the apartheid in health care between rich and poor countries, and between the rich and poor within countries, more profoundly than anything previously seen in medicine.
There is one overarching positive message for developing countries from the genome project. Though we are all virtually biologically identical, each of us is also unique. Tiny genetic differences exist between any two individuals, but these differences are no greater between people of different races than between those of the same racial background.8 The unravelling of the human genome has thus removed for ever any biological basis for racial discrimination.