The storming of the Bastille, on 14 July 1789, precipitated the fall of Louis XVI and the French monarchy. It is a symbol of liberty, democracy and the struggle against oppression for the French people,who came to realize their own power - and rights - and the arbitrary nature of dynastic rule. This painting is by Claude Cholat. Photo provided by akg-images.

In the first part of this message, The War on Cancer, I commented on the seemingly inescapable conclusion that human warfare has its origins in the biological process of natural selection and, ironically, in the fact that humans have evolved as social animals. The success of the species, and the consequent expansion of human populations, has led to a situation in which dozens of violent conflicts are occurring constantly in various parts of the globe. Yet well before the modern era, the biological rationale for intergroup competition - the promotion of the survival of a particular gene pool - had been essentially negated. Competition among our hunter-gatherer ancestors was between different tribes or tribal groups (i.e., genetically distinguishable peoples) occupying adjacent territory. Although genetic differences may be expressed in physical features, these, judging from the bitter conflicts between different religious groups within the same ethnic group, or between branches of the same dynasty, may not be of greater importance as a means of defining “us” versus “them” than differences in dress, customs, speech or beliefs. In fact the extensive mingling of peoples of different ethnic origins in the modern political territories referred to as countries, which have emerged (although many boundaries remain unstable) after millennia of conflict and colonization, has markedly diminished the original close relationship between territory and genetic homogeneity, and consequently blurred the distinction between competition for leadership within a group and competition between groups. In the modern world, an individual may simultaneously be a member of a “national,” ethnic, religious, socioeconomic, political, language or other group, any of which may provide a pretext for the establishment of a new hierarchical structure (“pecking order”) extending over as much territory as possible. Thus, cultural evolution, through its success, has both heightened the likelihood of conflict, and dramatically escalated its negative consequences. And whereas in the small, homogeneous tribal societies that constituted prehistoric mankind (remnants of which still survive), each individual had an important and recognized role to play within the single community, in the large, heterogeneous societies which emerged in the historical era, rulers, or ruling classes, have often been of different national, religious or ethnic origin, or, after the accumulation of vast riches, have perceived their subjects as inferior, and hence, fair game for exploitation. In late 18^th century Europe, centuries of oppression of the masses finally erupted into violent revolution, its epicenter in France, eventually resulting, in spite of strenuous opposition, in a permanent shift in the relationship between the people and their rulers - at that time the crown, nobility and the church.

The industrial revolution led to the exploitation of vulnerable populations, including women and children (children are shown here working in a coal mine). In addition to long hours, minimal wages and dreadful work environments, the lack of safety regulations led to frequent injury and death and a markedly increased risk of various chronic diseases, including, in some circumstances, cancer. Such exploitation continues in many world regions to the present day, even where prohibited by law. Photograph by Lewis Hine, Courtesy of the National Archives and Records Service.

These sociopolitical upheavals were fostered by more efficient, mechanized agricultural techniques which resulted in dramatic population growth. Simultaneous industrialization caused a major shift in populations from the countryside to the cities. New technologies required an educated populace, resulting in the rapid growth of the middle classes whose upper echelons themselves acquired enormous wealth and eventually seized the reigns of power. At the same time, the insatiable demand for iron, steel and coal to create and drive the engines of the industrial revolution, coupled to large-scale manufacturing in the cities, led to inhuman working conditions, overcrowding, exploitation of women and children (see photograph) and indescribable squalor in the rapidly enlarging urban slums. Occupational diseases, among them, cancer, and raging epidemics (six pandemics of cholera occurred between 1817 and 1923) led to a recognition of the importance of public health, epitomized by Disraeli’s Public Health Act of 1875, which required local authorities to ensure efficient sewage treatment, drainage and water supply. While Europe and her colonies (or former colonies) were in the vanguard of the political and technological revolution, the rest of the world has followed, and a survey of developing countries reveals a broad range of political and social circumstances not unlike those which existed in Europe at some point in the course of the last two to three centuries - although modified by the intrusion, to varying degrees, of modern technology and other aspects of “westernization.”

In Europe, the concept of government by consent of the people, whose antecedents extend to the ancient world, eventually prevailed over the idea of absolute monarchy (although not without enormous bloodshed), and along with it, the emergence of the idea that all people have rights, i.e., protection against the power of those who rule them. The French revolutionaries did not invent the concept, but in their Declaration of the Rights of Man and the Citizen, in 1789, went further than the constructs contained in the English Bill of Rights of 1689 and the Bill of Rights of the USA, also ratified in 1789. The seventeen articles of the French Declaration included the declaration that men are born free and have a right to remain free and equal in rights, protection against oppression, including arbitrary detention and inhuman punishment, freedom to practice any religion and to express their own opinions, the right of citizens to approve the purposes, levels and extent of taxation, and the right of society to hold all public servants to account. In 1794, additional social and economic rights were added, including the abolition of slavery and the statement that “public assistance is a sacred obligation.” In 1948, the United Nations published the Universal Declaration of Human Rights, based on international consensus, which includes the additional rights to education and a standard of living adequate for health and well-being, including food, clothing, housing, medical care and necessary social services. Unfortunately, declarations do not guarantee the rights they advocate. The French Revolution was followed by waves of terror, mass killings and a taste for the guillotine, while in many developing countries today, poverty is of such a degree as to exclude the possibility of education and health care, or even clean water, adequate food, clothing, and housing, for a large sector of the community. And it is still the case that what is seen as liberation from oppression by the many is often considered to be synonymous with mob rule by those who benefit most from the status quo.

Sociopolitical issues, although not usually considered the domain of health professionals, are critical determinants of public health - influencing both the causes of disease, and the effectiveness of disease control. Governments determine the priorities in spending public money, and are responsible, to a large degree, for the institutions of a country (sometimes developed over hundreds of years, but potentially wiped out in an instant). They are also responsible for security, education and health policy - all of which are both dependent upon and contribute, to the economy. Perhaps the central issue that the governments of developing countries must grapple with is the disparity between the size of the population and the size of the economy, a problem compounded by enormous inequalities with respect to the distribution of national and global wealth. This has an impact upon the quality and quantity of health facilities and health professionals and is largely manifested as a lack of access to health information and health interventions. Cancer, which comprises a set of complex diseases, is particularly hard hit - some patients never receive appropriate care while others present at an advanced stage, when treatment, if feasible, is more costly, complex and toxic. In the context of already inadequate resources, access to care for other patients is reduced even further (a situation I have referred to elsewhere as a “vicious cycle” ^[1]). Most patients do not even receive palliative care (symptomatic relief and emotional comfort), and die in abject misery. The challenge of solving these problems can only be met by increasing the capacity for controlling cancer through prevention, specific treatment and palliative care. This requires political will, i.e., the designation of health, including non- communicable diseases, as a political priority, and the development of the necessary funding to create additional resources. The capacity, however, to deliver sufficient health care can only be built through broad cooperation within and between

Building the capacity necessary to exploit existing knowledge and to continuously acquire more, is the key to cancer control.

countries and through the use of science and technology. The use of the latter to reduce the sum total of human misery, rather than contribute to it, should surely be a goal for the 21^st century.

Addressing the Problem of Limited Resources Through Building Capacity

Preventing Preventable Cancers and Curing Curable Cancers

Many of the deaths from cancer could be avoided by more efficient prevention or early detection. Some cancers (e.g., pediatric cancers, some leukemias and lymphomas, testicular cancers and trophoblastic tumors), are potentially curable by chemotherapy or combined modality therapy even when advanced. Yet prevention, early detection and chemotherapy are often the least available interventions in developing countries. Clearly, if preventable cancers are to be prevented and curable cancers cured, there must be increased emphasis - in locally relevant cancers - on these three approaches. Chemotherapy requires a skilled team of professionals and a broad range of hospital facilities, many of which span disciplines (e.g. microbiology and blood transfusion). Prevention and early detection require rather minimal resources, but could significantly reduce the burden of advanced disease, thereby improving patient access to care and helping to break the vicious cycle. Whether the approach (which depends upon the cancer in question) is via education or screening, cost-effectiveness is achieved when there is a high incidence of a preventable or easily detectable early stage cancer (i.e., one occurring in readily accessible anatomical sites), in a defined population group. Effective programs, however, require high population coverage, and therefore knowledge of the most effective means of promoting the program locally. Widely advertised screening programs also help to spread the message that cancer can be prevented and cured if detected early enough - a message that must be repeatedly emphasized to the general public, and also to health care providers and policy makers. Finally, screening also provides opportunities for the education of captive and receptive audiences (both participants and their families) as well as trainee care givers, and has an additional positive impact through the inevitable detection of, and opportunity to treat, benign diseases.

Figure 1. Successful model programs show “proof of principle” and define the costbenefit ratio. In addition to their intrinsic value, they provide convincing grounds for governments and donors to support their replication, which will extend their benefits to a wider constituency, the ultimate goal being adequate population coverage.

Increasing the Efficiency of Existing Facilities

A variety of individuals and institutions are involved in the care of cancer patients, ranging from solo practices to major cancer centers. In general, oncological services are poorly coordinated and largely devoid of quality control. Efficiency would be greatly increased by the development of regional networks for cancer services. Peripheral centers and even temporary clinics could participate in region-wide screening, educational programs and palliative care; patients with suspected invasive cancer would be immediately referred to a competent treatment facility. Ancillary health professionals can be quickly trained to undertake much of the screening and public education, thus lessening the load on specialists. The regional plan may involve central confirmation of diagnosis, standardization of care plans, continuing education programs and outcome measures. Treatment of early-stage cancer may be conducted in a general hospital (by a visiting specialist if need be). More complex cancer surgery, radiation therapy and chemotherapy should be conducted only in an appropriately equipped and staffed cancer center. Regional planning will normally involve governments, and a coordinating cancer control committee, and should be based, where possible, on successful pilot or model programs (Figure 1).

Increasing the Number of Health Professionals and Cancer Specialists

Since developing countries suffer from a shortage of health professionals, more doctors and nurses must be trained, some of whom will go on to specialize in caring for cancer patients. Medical and nursing schools can be established with quite minimal facilities, while the shortfall in teachers can be compensated for by the use of information technology and visiting experts. During their training, medical students (and nurses) should be made aware of the importance of encouraging their patients to live a healthy lifestyle and providing information regarding the prevention and early diagnosis of cancer - primary health care providers have a major role to play in these areas.

Figure 2. Development of cancer centers in countries with minimal resources will involve building new specialized cancer hospitals and research units (preferably to a standard design, to reduce costs), or use of suitable existing premises, the training of staff and the introduction of relevant foundation programs.

Establishing more Facilities for Cancer Prevention and Treatment

In many of the poorer countries, a high proportion of cancer care is provided by general surgeons in general hospitals. There is clearly a need to expand the number of specialized cancer centers and units, and in addition, the number of prevention programs, trained cancer surgeons, radiotherapy facilities, chemotherapists and palliative care programs (Figure 2). Continuing education systems will be required for existing health care staff and the establishment of training programs in cancer prevention - almost non-existent anywhere - would ensure that this element of cancer control is emphasized. While poor countries cannot afford to provide either enough facilities or the needed experts to staff them, structural factors in their medical professions compound the problem - including poor working conditions, limited possibilities or incentive for research, seniority rather than merit-based professional advancement, and low salaries. This results in many of the more ambitious and more expert staff members moving to the private sector, or to more affluent countries, further reducing resources available to poor patients. Many young people are sent for or seek training in affluent countries on the assumption that their education will be superior. While this is often true, such training is costly and many trainees never return, preferring the professional and economic advantages abroad. Those who do return often find that their training does not equip them to deal with the high patient burden, limited resources, and more advanced, or sometimes quite different diseases they encounter in their own country, creating disillusionment and a strong desire to return to the affluent world. The expansion and improvement of cancer centers in developing countries, then, is important not only from the perspective of increasing access to care, but also to providing more training centers and improving opportunities for young professionals in their own countries, thereby reducing the constant loss of talent.

In-country training programs, however, must address the problems of the quality and quantity of existing educational facilities. One solution is to provide broader access to expertise within and outside the country. Visiting experts may participate not only in the teaching of young trainees, but in continuing education of all staff, a process that can be supplemented by an organized program of workshops, symposia and training courses, supplemented by telemedicine programs and e-learning (see below). Multiple expert visits can be associated with needs assessments and the provision of more tailored educational experiences as well as the introduction of modern approaches and technologies that will improve efficiency (compensating for the limited human capital and potentially reducing cost). Visiting experts benefit from the broader clinical experience, and may stimulate collaborative research projects. In circumstances where such in-country training is not possible, the next best alternative is training in good quality programs in countries with similar socioeconomic status and cancer patterns. This may benefit both trainer and trainee and reduces the risk of migration.

Developing Relevant Cancer Control Programs

While the increase in quality and quantity of health professionals will inevitably improve cancer control, it is essential in all countries that maximal efficiency is achieved with respect to the translation of resources into health benefits. This requires effective organization. Ideally, a master plan for capacity building should be combined with the development of a cancer control program (as advocated by the World Health Organization) based on knowledge of the regional cancer pattern (where possible, via population- based registration) and the distribution of resources. It should also be integrated into the overall health plan. Where resources are particularly limited, the selection of a small group of (priority) programs in each of the areas of prevention, early detection, radiotherapy, surgery (where expertise is lacking), palliative care and if possible, chemotherapy (for at least one potentially curable disease) will provide an excellent foundation on which to build (Figure 2). Priority programs should be chosen on the basis of the incidence or frequency of preventable or curable cancers, and should include realistic goals. As time passes, and particularly if programs are successful, priorities may change. Maximal benefit is likely to be achieved when educational service and research elements are combined, and when multiple benefits are gained from each program, e.g., through providing information to accompanying family members, demonstrating successful programs to other professionals and trainees, and ensuring replication and dissemination to other parts of the country or region.

The Importance of Clinical Trials

Regionally relevant research is an important element of cancer control, and clinical studies, including surveys, prevention and treatment trials, should be undertaken whenever possible, led by, or in collaboration with experienced clinical researchers - where necessary from outside organizations. Such trials, in their simplest form, consist of the disciplined application of appropriate treatment (or prevention) guidelines coupled to outcome measures, but may also include translational research elements. They should lead to an immediate improvement in patient management and provide a focus for “hands-on” training of a broad range of health professionals, not only in research - which is essential for the improved definition and solution of local problems, and stimulation of a more enquiring mind-set - but also in good medical practice (Figure 3). Where such trials involve multiple centers (cooperative groups) in the same or different countries, they also lead to sharing of available expertise and educational opportunities for young and experienced staff alike, and can be coupled with the creation of scientific resources, such as tissue banks. The desire for an enhanced professional reputation creates added incentives for improving the quality of care, and high-quality data provides a foundation of evidence relevant to national or regional problems on which to build ever more efficient cancer control strategies.

Figure 3. Clinical trials, particularly if multicentric, have multiple values beyond the specific research being undertaken. In addition to the “on-the-job” training for various staff members, physicians become more familiar with the scientific method that should inform their clinical practice. Finally, when research is combined with cancer prevention or management, patients derive immediate benefit.

The Role of Information Technology

Modern information technology can enhance all aspects of communication, including consultations, education (e.g., through multi-disciplinary telemedicine conferences and a variety of e-learning tools), knowledge assessment, record keeping (including registration and clinical trials data management) and access to data and images. Information technology is in.expensive compared, for example, to imaging or radiotherapy equipment and in addition to increased efficiency and reduced costs (by decreasing time and staffing requirements) improves access to expertise (national or international) and information. It can also greatly improve the efficiency of patient tracking and follow up and through bar coded drugs or products and automatic label generation, improve treatment documentation and reduce errors in patient care.

Developing Financial Support

Few governments in developing countries can afford to support the construction of the required number of cancer centers, so that the necessary resources, at least in the short term, must largely come from elsewhere, such as non-profit, non-governmental organizations (e.g., INCTR), international organizations (e.g., the United Nations and its agencies), and foreign governments, Responsible corporations have an important role to play, since they provide products necessary for cancer control, and their interests are also served by increasing access to (i.e., use of) their products - ideally, through promoting education and training. All such outside organizations must work closely with local governments, institutions and organizations and must not automatically assume that “western” methods are best - planning must take account of social, economic and cultural differences as well as the resultant differences in the pattern of cancer. Alliances of organizations interested in cancer control and/or in promoting development may make valuable contributions. Truly global strategies may be possible when universally applicable preventive strategies exist (e.g., tobacco control, such as the Global Tobacco Framework, and vaccines against infections associated with cancer), and these may have multiple health benefits.

Developing countries tend not to have health insurance schemes, at least for the poorer members of society who can barely survive today, and consequently have limited ability to put aside resources for tomorrow. This must change, with means-based systems, and return on expenditure for the insured (e.g., education and screening)^[2]. Successful prevention will, of course, render the insurance program more cost effective. Insurance schemes can also result in significant redistribution of health care costs, creating a more equitable sociopolitical environment, and reducing dependence upon external resources. Ideally, insurance should cover at least some of the costs of relevant research - which is justifiable on the basis of its potential for further reducing the cost of care.

Epilogue

One can only wonder whether the collective human mind will eventually learn to control its potentially fatal instinctive drive to compete violently with perceived “others” and instead, to devote more energy towards promoting its equally instinctive cooperative element, to the benefit of global security and the reduction of poverty, environmental degradation and disease. This will require a more inclusive sense of “us”, and a real attempt to find ways to reverse the present gross (and increasing) inequities in the world, for these are the lifeblood of insecurity and conflict. Cancer is a common threat to the world's people, and as such will be more effectively addressed by concerted action. The 21^st century holds great promise of ever more rapid scientific advance, and the discovery of highly effective, minimally toxic and less expensive approaches to the prevention, diagnosis and treatment of cancer. Developing coun.tries, which account for 85% of the world’s people and a continuously increasing fraction of its cancer, can contribute greatly to this process as well as benefit from it, and their exclusion, or incomplete participation, will be to the detriment of all. Such countries contain enormous reservoirs of human talent, and with their vast range of genetic and environmental patterns, provide unique opportunities for scientific research. Helping to build.ing capacity for cancer prevention, treatment and research in such countries is the surest way to ensure that suffering and death from cancer throughout the world will be dramati.cally decreased in the coming years.

References:

^[1] Magrath I. Chemotherapy in Developing Countries – is less better? European Journal of Cancer; 2003: 39, 1497-1500.

^[2] Insurance has been included in the 10 elements of a Grand Strategy to Control Cancer listed in the first part of this message - see electronic version on www. inctr.org/publications/network.shtml