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Fifty years of the International Agency for Research on Cancer (1965 to 2015)

2015; Wiley; Volume: 138; Issue: 6 Linguagem: Inglês

10.1002/ijc.29929

1097-0215

Rodolfo Saracci, Christopher P. Wild,

Nutrition, Genetics, and Disease

On 20 May 1965 the World Health Assembly, convened for its annual session in the United Nations building in Geneva, established the International Agency for Research on Cancer (IARC) as an autonomous research agency within the framework of the World Health Organization (WHO). It was the start of a successful endeavour in international collaborative research focused on cancer prevention1. Viewed today, the early 1960s appear not far from nor unconnected to World War II. The long aftermath of conflict, extending into the mid-1970's, was a 'golden' period of reconstruction and economic expansion, with increasing opportunities and well-being for all people. A spirit of solidarity, prompted by the harsh experience of war, had generated within and between nations a momentum of international cooperation that succeeded in overcoming the deep ideological and political contrasts of the "cold war" and in keeping in check the spectre of nuclear conflict. The United Nations Organization had been established in 1945 and its specialized agency for health, the WHO, in 1948. The roots of IARC can be traced to this post-war context but the catalyst was wrought by an individual act of conviction. In 1963 a journalist based in Nice, Yves Poggioli, deeply affected by the suffering of his wife after a cancer diagnosis had initiated efforts to create an international centre to fight cancer: the proposal was to finance the venture by transferring resources from national budgets destined for nuclear armament. In early April 1963 Poggioli wrote a letter to a newspaper editor and fellow member of the French 'Movement for Peace' asking him to forward his idea to the World Peace Council (another organization working for nuclear disarmament).The editor, Emmanuel d'Astier de la Vigerie had enlisted in the French Navy at the onset of World War II. After the fall of France in June 1940 he was an early entrant into the French resistance movement using his journalistic experience to produce the underground newspaper Liberation. The letter from Poggioli weighed heavily on him, asking him as it did to pause from his political battles to consider the question: "What are we doing to fight cancer?" As D'Astier's wartime connections included General Charles de Gaulle, it is not surprising that he decided to directly approach the now President of the French Republic, proposing the creation of an international cancer agency. Having first spoken to de Gaulle, he strengthened and detailed the proposition with an open letter, copied to the embassies of the United Kingdom, USA and USSR, co-signed by twelve French leading personalities including the biologist Jean Rostand and the highly distinguished cancer specialist Antoine Lacassagne, president of the French League against Cancer. The open letter called for a "derisory" 0.5% of the military budgets of the USA, USSR, United Kingdom and France to be invested in an international cancer institution under the auspices of the United Nations and engaged in a "fight for life" against "one of the greatest scourges weighing on humanity". Positive reverberations followed the letter, a headline in the New York Times reading "Use of Arms Funds on Cancer is Urged". In response a cascade of swift actions came from the French government, initiated by de Gaulle, leading to contacts with Ministers of other countries and the WHO. Progress was made at an astounding pace. Less than eighteen months elapsed between the open letter (in November 1963) and the establishment of IARC by the more than 100 countries of the WHO General Assembly (May 1965). The intense exchanges of that period, the sequence of meetings and the actions and reactions of the various involved parties have been reported in detail.2 (Also available in English http://www.iarc.fr/en/publications/pdfs-online/treport-pub/treport-pub6/index.php) France, as initiator, was the obvious location for the newly established agency. Lyon was selected as the host city, both by virtue of its proximity to WHO Headquarters in Geneva and, crucially, because of a strong engagement from the Lyonnaise scientific and medical community and the enlightened and energetic Mayor of Lyon, M. Louis Pradel. The initial proposal of endowing the agency with funds at the level of 0.5% of the defence budgets of the major military powers (roughly 380 million USD annually) had been vastly scaled down, through successive discussions between governments and WHO, to just over 1.0m USD. The Agency would have its own independent governing body comprised of representatives of its Participating States, which would approve the strategy, the budget and elect the Director. The Agency terms of reference broadly covered cancer research, albeit IARC would not be involved in issuing policy recommendations, a task statutorily belonging to WHO. The institutional and financial foundations of the new organization having been laid down, three major tasks remained: to design a scientific programme; to have the programme transformed into research projects by an internationally recruited staff; and to secure the necessary technical facilities and physical premises. John Higginson (1922–2013) was appointed the founding Director of IARC on 1 July 1966 and provided the vision and vigour, not disconnected from much-needed diplomacy, to address all three tasks. At the time of his appointment he was professor of Geographical Pathology at the University of Kansas, USA. His pioneering 1953–55 survey, combining pathology and epidemiology, on the Bantu and "Cape Coloured" populations in Johannesburg, South Africa3 documented the differences - often substantial - in the incidence of many cancers compared to Western populations. This evidence buttressed the suggestion emerging from worldwide comparisons of cancer mortality rates between populations, that differences in environment are likely to play a major role in cancer causation. Geographical pathology, appreciated by Higginson from his prior international experience, was to be a key consideration in shaping the new agency. Diverging views had been expressed by representatives of the countries involved about the suitability of having laboratories included within the new organization. One view held that the agency should be focused on and limited to epidemiology. Higginson considered that laboratories should be an integral part of IARC. This had two key advantages. First, it favoured the incorporation of laboratory tests into epidemiological studies, a feature of growing importance with the development of biomarkers of exposure, susceptibility, and early lesions measurable in humans. Second, placing epidemiologists and scientists carrying out experimental research under the same roof enabled IARC to stay at the frontiers of cancer research. Thus the far-sighted determination of John Higginson enabled IARC to pioneer molecular cancer epidemiology and to incorporate the latest understanding of cancer biology into studies of the causes and prevention of human cancer. Among the very first work programmes of the new agency, two soon became IARC trade-marks, producing publications widely recognized as key references. The first was the series "Cancer Incidence in Five Continents", developed under the committed leadership of Calum Muir (1930–1995), resulting from systematic reporting of cancer incidence data from registries worldwide. This was complemented by technical and financial support to cancer registries in order to improve the quality and coverage of registries worldwide. The second was the "IARC Monographs on the Evaluation of Carcinogenic Risks to Humans", the brainchild of Lorenzo Tomatis (1929–2007), the second IARC Director, consisting of systematic critical reviews and evaluations of the carcinogenic potential of agents to which humans are exposed in their environment. The IARC Monographs have become key reference tools for regulatory authorities in many countries and for other international organizations. Another founding role of IARC was based on the recognized need to help train cancer researchers worldwide; training fellowships and courses having been one of the consistent features of the Agency. With an inter-disciplinary approach embedded into its fabric and its emphasis on international collaboration, IARC's creation gave rise to several innovative research projects, such as investigations of liver cancer in relation to aflatoxin exposure in Africa, studies on EBV virus in the etiology of Burkitt's lymphoma, research exploring the causes of the high frequency of esophageal cancer in the Caspian Littoral in Iran and, later, the multi-centre European Prospective Investigation into Cancer and Nutrition comprising a cohort of more than half a million participants across ten countries and including a novel biobank with around 4 million biospecimens. The three former projects were forerunners of some of IARC's greatest achievements in developing countries, notably the studies confirming human papillomaviruses as the cause of cervical cancer, the long-term vaccination trial to prevent chronic hepatitis and liver cancer in The Gambia and studies evaluating the effectiveness of simplified screening for cervical cancer in India. The history of IARC's development and a large spectrum of scientific contributions made through collaborative research with many thousands of colleagues worldwide are the subject of a recently published book.1 Its 260 pages include short quotations extracted from a series of interviews with some of the key figures from IARC's past while the scientific content is provided against a background describing the general medical, public health and societal contexts in which IARC operated at the time and continues to operate today. In 2015, cancer remains a global health problem. As a result of population growth, increasing life expectancies and changes in underlying incidence, the annual number of cases continues to rise worldwide, being expected to increase by around 60% in the next 20 years. However, the distribution of cancer is shifting, with the largest relative increases in new cases set to occur in developing countries along with increases in other non-communicable diseases. This is a consequence of demographic changes and the spread of major cancer-causing agents like tobacco use, alcohol consumption, and obesity combined with the adoption of sedentary habits at home, at work, and in transportation which add to the existing burden of risk factors such as chronic infections. As a result, many developing countries are now confronted with the double burden of communicable diseases and malnutrition together with a rising incidence of non-communicable diseases, including cancers. IARC has always had a role in studying cancer in developing countries, but this "cancer transition" adds to the motives. At the time when IARC was established initiatives were frequently driven by scientific interest, arising from special patterns of cancer occurrence and the associated opportunities to understand causes viewed through an international lens. The new epidemiological situation means the emphasis is expanding to support developing countries in their efforts to tackle the new major public health challenges. Improving the effectiveness of cancer diagnostic and treatment services is a priority. Yet the cancer problem cannot be solved in this way in any country if nothing else because of soaring costs of effective treatments. This perspective provides compelling reasons for supporting prevention, aimed at curtailing the number of cancers by avoiding their occurrence. When IARC was founded in 1965, prevention was recognized as the key avenue towards cancer control because cancer treatments had definite but limited scope. Now the escalating costs of cancer treatments – effective, or just promising – point again to prevention as the cornerstone of cancer control. IARC, an institution of comparatively modest size (about 300 people, with a core annual budget provided by 25 governments of around 20 million euros), has become an international leader in cancer research because since its earliest days IARC's scientific programme has been designed to produce "knowledge for prevention". This work now extends from identification of the causes, through evaluating preventive interventions to studying their implementation in public health and health services settings. The IARC commitment to 'health for all' through prevention has been successfully maintained thanks to excellent scientific staff committed to cancer research and to public health, both pursued independently from extraneous interests and pressures. This core scientific staff has benefitted from dedicated support staff in-house and thousands of scientific collaborators across the world. Fifty years on, the IARC model of international collaborative research is not simply valid but necessary: international studies are increasingly needed to answer national questions of cancer control. IARC's autonomy, high-quality work, integrity and reputation allow it to provide the reliable evidence-base on which decision-makers can confidently base guidelines, recommendations and policy. Further, IARC provides an example of what is achieved when people of different nationalities and from different cultures cooperate together towards a common goal for the betterment of the human condition. Charles de Gaulle, in his first references to the new agency pointed to three features he hoped it would embody: cooperation between peoples, improvement of the human condition and advancement of science. While anchored firmly in the scientific activities of cancer prevention and control, IARC strives to fulfil the ideals envisaged by the pioneers of 50 years ago. Rodolfo Saracci and Christopher P. Wild International Agency for Research on Cancer, 150 cours Albert-Thomas, 69008, Lyon, France