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I.9   The Biological Revolution and
its Implications for Health


Unravelling the human genome. Epidemics and infectious diseases. Hereditary disorders. Longevity. New challenges, new approaches. Opportunities and needs for biotechnological development and international cooperation. The brain and neurological disorders.

Chair: Jorge Allende Director, Instituto de Ciencias Biomédicas, University of Chile, Chile
Rapporteur: Nicole Biros Director, Research Policy and Co-operation, WHO

Session co-ordinator: Nicole Biros Director, Research Policy and Co-operation, WHO
Local secretary: tbd


The biological revolution and
its implications for health: an overview

Jorge E. Allende
Director, Instituto de Ciencias Biomédicas, Facultad de Medicina, University of Chile, Chile

The new millenium finds us in the midst of a biological revolution driven by the explosive advances of genetics and molecular biology of the last half-century. This revolution has given the power to mankind to alter the course of evolution and to mold the stuff of life. The whole sequence of the human genome is only a few months away and the deluge of information about genes, proteins and their interactions in beyond the grasp of the human mind.

This revolution entails a change in the way we will have to conduct research and in the way we interpret the results of that research since it will be necessary to address the immense complexity of the whole living cell or of a complete organism to draw valid conclusions as to the function of each molecular component of the life process. These changes require also a new way of training our student, giving emphasis to integrative capacities and to a broader knowledge that can find correlation's and patterns within the incredibly complex circuitry's of the cellular metabolic pathways.

As scientists we are convinced that knowledge is good and that the post genomic era of biology will result in a much more profound understanding of the fascinating mysteries of the phenomenon of life, of our own nature and of our cognitive capacities. The benefits of this knowledge and understanding should be especially evident in medicine, where the genetic basis of many diseases will become clear and where new therapies for old and new maladies will bring relief from suffering to millions of individuals. The genomics of microorganisms will give us new tools to combat old or emerging infectious agents and pharmacogenomics will give to the design of drugs tailor-made for the genetic characteristics of each patient. The knowledge of the genetic health risk factors of individuals at birth should result in careful monitoring and more efficient medical treatments.

This hopeful and optimistic picture, however, is darkened by the fact that the benefits of science and technology, especially those in the biomedical area, will not reach all of human kind. The millions of poor in the developing world will continue to suffer the devastating effects of the diseases for which science will have found cures unless we, scientists and political leaders, do something drastic. An effort has to be made to stimulate health research in the developing world and to direct the enormous global scientific capacity to focus on the illnesses that attack the vast populations of this area of our interconnected globe. In addition, the local and international political leaders will have to find solutions to a demand that has to meet the basic human right to health.

Our social responsibility demands that we share the grate benefits that scientific knowledge produces and that we actively participate to ensure that the use of this knowledge is both ethical and equitable.

Genetics and health

Maxine Singer
President, Carnegie Institution of Washington, USA

The roots of the current revolution in biology are found in fundamental research in biochemistry and microbial genetics. Those carrying out this work in mid-century could not foresee the extraordinary current developments. They were motivated by human curiosity. Among the profound outcomes of their research was the demonstration of the universality of genetic mechanisms and molecules among all organisms. Consequently, current work with model organisms such as yeast, worms, flies, and mice is essential to understanding human biology and applying that understanding to the improvement of human health. Plants too share the common genetic mechanisms and research on plants is central to advancing the human condition. The various Genome Projects, aimed at determining the entire DNA sequence of the genomes of humans, the model organisms, and selected other species, will contribute greatly, and in unanticipated ways to the health of people worldwide.

A great deal of new science has been and will be required if the new knowledge of genetics is to fulfill its promise. The genetic and molecular components of many diseases are being characterized. The molecular aspects of aging are being studied with the hope of improving people’s late years. Diagnostic techniques for inherited diseases and cancers are steadily increasing and being improved. Vaccines and therapeutic materials obtained through genetic engineering are already available and many others are on their way. Progress is being made in the difficult area of gene therapy.

The ability to screen for particular gene alleles will profoundly affect the medicine of the future. Treatment of disease will be advanced by improved diagnoses. Eventually, individualized therapeutic approaches will become possible as the unique reactions of individuals to particular therapies become predictable. Similarly, the unique genetic properties of tumors will recommend highly focused treatments.

Perhaps even more important in the long term are developments that can benefit whole communities rather than individuals. Genetic screening techniques provide rapid, precise ways to analyze foods for contamination by pathogens and determine the cause of incipient epidemics. Environmental issues such as the purification of contaminated land and water supplies are also being addressed. The availability of sufficient, safe food in places where it is needed is a continuing challenge. Plants genetics is beginning to address this important problem by developing plants for increased agricultural productivity, especially in relatively infertile areas including those where fresh water is limiting. Green plants are the one efficient and renewable way to use directly the sun’s energy. These approaches could decrease dependence on fossil fuels and the pollution they cause. They can also permit conservation of land in a natural state hospitable to other animals and plants.

People worldwide will want to take advantage of these benefits. To do so will require thoughtful discussion of the related personal, social, and ecological questions they raise and the development of scientifically sound approaches to their use and regulation.

Vaccines for the future

Paul-Henri Lambert
WHO Adviser for Vaccine Research, Belgium/Switzerland

Vaccines and vaccination are at a turning point. Although vaccination has been demonstrated as the most effective way to prevent infectious diseases, its major public health impact has been restricted to the control of a limited number of human diseases including smallpox, poliomyelitis, neonatal tetanus, diphtheria, pertussis, or measles. Vaccines currently in clinical use have been developed through relatively simple, largely empirical approaches. However, recent advances in microbial genetics and in immunology have opened the way towards a revolution in "vaccinology", and new vaccine strategies based on the understanding of microbial pathogenesis and of host defence mechanisms emerge.

Within the next 10 to 15 years, a whole set of new preventive vaccines against infectious diseases or neoplasm, and some therapeutic vaccines should become available. Their potential impact on global mortality due to infectious diseases could reach 9 million prevented deaths per year, if new vaccines against pneumonia, meningitis, diarrhoea diseases, malaria, tuberculosis and possibly AIDS, would become available.

After the progressive introduction of hepatitis B immunisation and its preventive effects on liver cancer, the benefit of vaccination should also be extended in the near future to the prevention of cancers associated with Helicobacter pylori (55% of stomach cancers) and with papilloma viruses (over 80% of endocervical cancers). Some other cancer vaccines based on the use of tumour antigens (e.g. melanoma) have now entered the phase of clinical trials. Therapeutic vaccines that aim at restoring a " normal " immune response to major allergens are already produced against increasingly prevalent allergic diseases whereas preventive and therapeutic peptide vaccines for autoimmune diseases are on the drawing board.

Progress in microbial genetics and advances in genetic engineering are an essential part in the ongoing vaccine revolution. Identifying the molecular basis of virulence and microbial antigens essential for the induction of successful host defence mechanisms allows the construction of " intelligent " vaccines, such as genetically engineered attenuated micro-organisms or live vectors carrying foreign genes relevant for protection. Attenuated strains can also be used as vectors carrying foreign genes into their bacterial genome. Deciphering of the entire genomes of most important human pathogens will also have a marked impact on vaccine development.

Understanding protective mechanisms, i.e. molecular processes involved in the immunological recognition of microbial antigens and in the differentiation of cells which mediate effector mechanisms are generally required for the design of new vaccines against diseases for which an empirical vaccination approach has failed. In order to be protective, vaccines should be designed to elicit appropriate protective immunological effects. Whereas antibody responses are sufficient to protect from infections by pneumococci or meningococci, additional cellular responses are usually needed to prevent diseases caused by intracellular microorganisms such as viruses, chlamydiae, certain bacteria (mycobacteria) or parasites (malaria, leishmania), capable to hide and survive within the environment of the infected cells. It is now becoming feasible to design vaccine formulations which can polarize vaccine-induced responses towards a desired pattern.

However, the increasing availability of new vaccines raises issues, which limit their introduction into routine use. A number of parents are already concerned about the high number of vaccines administered to their young infants and even vaccines that have already been demonstrated for years to be both efficient and are not being optimally used to protect those who need it most. As vaccine-related adverse events may become more visible than some vaccine-preventable diseases, efforts to maintain a high level of vaccination coverage for the benefit of the community are often jeopardised by organised efforts of opponents to immunisation. Finally, major obstacles towards the global use of new vaccines are of an economic nature.

The biological revolution: what’s in it for Africa?
La révolution biologique: quels enjeux pour l'Afrique?

Mireille David-Prince
Université du Bénin, Togo

En matière de santé, l'Afrique se doit de relever de grands défis, par la mise en œuvre de stratégies de lutte contre les maladies touchant les populations entières à l'échelle du continent, et ce dans un contexte socioculturel et économique assez difficile. Ainsi très tôt les autorités politiques et sanitaires des pays Africains ont opté pour le développement d'une médecine préventive au détriment d'une médecine curative. La révolution provoquée par l'application des concepts et des techniques de biologie moléculaire en médecine a t-elle permis d'envisager pour l'Afrique une médecine qui en recherchant l'origine des maladies au niveau du gène permet de prédire pour mieux prévenir et ainsi de faire régresser l'incidence de telle ou telle pathologie en traitant le mal le plutôt possible voire dès le début de la vie humaine. Depuis 1977-1978, date du premier clonage de gènes humains, les gènes de l'hémoglobine, l'Afrique noire où sévit sur une large échelle la drépanocytose, première hémoglobinopathie connue au monde a t-elle vraiment bénéficié des résultats et applications de cette découverte? Pourtant il paraît évident au chercheur Africain que nous sommes, que les populations Africaines ont réellement participé à la recherche mondiale en biologie moléculaire, voire ont été à l'origine d'importantes découvertes dans le domaine, dans la mesure où de grands fléaux, véritables problèmes de santé publique en Afrique, ont servi de modèles d'études du gène humain pour mieux comprendre la physiopathologie de maladies génétiques (drépanocytose S, C, thalassémie) ou de maladies infectieuses (hépatite B, VIH ...). A l'orée de l'an 2000 le chercheur Africain en biologie se pose encore beaucoup de questions :

  • Quel a été le bénéfice réel pour les populations du vieux continent des acquisitions nouvelles en génétique moléculaire?
  • Suffisamment de cadres et d'équipes ont-ils été formés pour poursuivre des recherches fiables (haut niveau de qualité, diffusion) dont les résultats seraient utilisables en vue d'une régression sensible de l'incidence de certaines maladies du continent. ?
  • La formation des cadres Africains dans les pays du Nord prend elle réellement en compte l'objectif de transfert de technologie pour une pérennisation des acquis et une poursuite d'une activité fructueuse?
  • Les budgets mis à disposition par les gouvernements pour la recherche sont-ils conséquents et en adéquation avec les besoins prioritaires des populations?
  • Existe t-il de réelles collaborations des équipes africaines avec celle des pays développés mieux nantis, pour une recherche en partenariat?
  • Les financements obtenus pour certains travaux en partenariat sont-ils suffisamment "promoteurs" pour les équipes du Sud? Après une analyse de la situation actuelle de la recherche en biologie moléculaire en Afrique sub-saharienne, nous envisagerons les stratégies possibles pour améliorer les performances des équipes de recherche pour une meilleure santé des populations.

The Biological Revolution and its Implications for Health.
New perspectives on ageing

Edit Beregi
Semmelweis Medical University, Hungary

At the end of the 20th century the most important demographic change is the increasing number of aged population as a result of advance in sciences and medicine. Longevity has become a striking feature of the 20th century. During this century, the average education level and socioeconomic conditions of the population have improved in addition advance in public health and in modern therapy resulted in better health and more activity of the elderly. We are living longer and working for a lesser number of years, therefore now a major concern would be to find social, cultural and recreational activities for the growing number of retired persons.

Unfortunately, improved life expectancy has not ensured freedom from diseases. The pattern of diseases changed. During the past years, the principal cause of death in the population shifted from infectious diseases towards chronic diseases. Chronic diseases will be the major health problem in the 21st century.

The 20th century was the century when scientific discoveries resulted in several basic and practical outcomes; the 20th century was beneficial for mankind, for aged people. The 21st century will be the century of the practical use of high technology by monitoring the health status, controlling diseases, eliminating environmental risks, and promoting disease prevention and health education. The scientific resources are greater now than ever in history. Human knowledge will lead to prolong healthy life span. If we can relate the new technologies with social and psychological support, which are equally important, we can look forward to a time when this advances combined will provide more opportunities for a meaningful existence late in life.

Application and implication of the cloning of a disease gene:
cystic fibrosis as an example

Lap-Chee Tsui
The Hospital for Sick Children; University of Toronto, Canada

The most important revolution in biomedical science in the last two decades has been our ability to isolate various disease-causing genes and study the basic defects at the molecular level. In my presentation, I would use the cloning of the gene for cystic fibrosis to illustrate various points. Cystic fibrosis is a common genetic disorder in the Caucasian population. Patients with CF suffer from a variety of problems associated with respiratory tract, gastrointestinal tract, male reproductive tract and other exocrine malfunctions, including loss of electrolytes in their sweat. Progressive airway disease is the primary cause of morbidity and mortality in CF. The isolation of the CF gene was accomplished in 1989. Significant progress has since been made regarding our understanding of CF in the past 10 years. The primary defect in CF has been attributed to the loss of a CAMP-activated Cl ion conductance and an up-regulation of sodium ion reabsorption from the secretory epithelium. The most common CF mutation is a 3-bp deletion ([delta]F508) which accounts for about 70% of CF chromosomes worldwide. In addition, there are over 800 other mutations that have been identified, although most of them are rare and some appear to be population specific. The mutation data have been widely applied in DNA diagnosis and carrier testing. The CF mutation database can be accessed through the Internet via the web site <>. In general, CF mutations could be divided into 5 major classes in term of their presumptive molecular consequence. The clinical presentation of CF is heterogeneous, however. Some of the variability could be explained by the spectrum of mutations. CFTR mutations have also been detected in a number of seemingly unrelated diseases, such as male infertility, including congenital bilateral absence of vas deferens and obstructive azoospermia, pancreatitis, and various pulmonary diseases, including chronic obstructive pulmonary disease and asthma. Unfortunately, it is difficult to offer prognosis to individual patients based on CFTR genotype alone. It is clear that the clinical heterogeneity of CF is not only determined by the genotype at the CFTR locus. Using a CF mouse model, we have recently mapped a major modifier gene locus for intestinal obstruction during their early life. The same modifier gene appears to exist among CF patients. More recently, by introducing the CFTR mutation into different genetic strains of mice, we have found that CF mice could develop lung and liver diseases. Therefore, through various approaches, we have gained a good understanding about cystic fibrosis since the cloning of the causative gene. CFTR mutation analysis has helped in understanding the etiology of some of the related diseases and led to practical use in genetic counseling. Clinical trials have been initiated from several fronts, including CF gene therapy, and correction of the misfolded [delta]F508 protein. Our work on the modifier genes has also opened up new means to develop novel strategies for CF treatment. It is anticipated that the human genome project would bring even more insight into many common diseases, such as asthma, diabetes, rheumatoid arthritis, and various neurological and mental illnesses, which afflict a much larger human population.


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