In 1935, Albert Einstein, Boris Podolsky and Nathan Rosen published a paper of pivotal importance in the evolution of quantum mechanics, one of the two major 20th century revolutions in physics. They drew attention to an apparent paradox of quantum theory (subsequently known as the EPR paradox) which predicts that two once-linked sub-atomic particles, no matter how far apart they travel, will remain forever entangled such that measuring a particular characteristic (e.g., the direction of spin, or polarization) of one of the particles will instantaneously result in the other “acquiring” a complementary characteristic. Despite Einstein's profound discomfort with the notion of “action at a distance,” leading him to suggest that quantum theory must be incomplete, experiments performed decades later have confirmed the theoretical prediction, and excluded the presence of local “hidden variables” that could account for the phenomenon. The particles behave as a unit. Entanglement has practical implications for the development of new technologies, such as quantum teleportation, quantum cryptography and quantum computing, but it has even greater implications for the reality behind the constructs of our senses. For whereas the macroscopic world we perceive appears to be comprised of individual elements (the ten thousand things) which are subject to the influence of local factors - a perspective that even Einstein was reluctant to discard - the reality is that all events are probabilistic - that is, they arise in the context of a vast interconnected and self-consistent web, fitting into place according to their probability of occurrence. Particles thus exist as “probability waves” with a certain amplitude (encompassing the range of possible locations) and become “real” only when a measurement is made - implying that the observer, and, therefore, consciousness, is an integral part of the system. These concepts - both the wave-particle duality and the influence of the observer - are difficult to grasp after centuries of Cartesian dualism (separation of mind and body), and Newtonian mechanics (whereby the cosmos is perceived as a giant deterministic machine - a clockwork universe put into motion by a god who is somehow separate from it), but have profound implications for the nature of the world in which we live.

The proposition that all particles are entangled is inherent in the big bang theory, according to which the Universe evolved from an infinitely small, infinitely curved and infinitely dense point, a singularity, which, some 15 billion years ago, released its contained energy in a tremendous explosion. From the resultant, rapidly expanding four dimensional web of electromagnetic vibrations particles emerged, eventually aggregating, in areas of sufficient density, into stars, which continue to recede rapidly from each other in the present-day Universe. This well substantiated theory, incidentally, relegates absolute rest and nothing to the status of purely relative concepts. Science has moved distinctly away from Aristotle's elaborate theory of causality and now sounds remarkably similar to the philosophical concepts of the great Eastern religions. Hindus and Buddhists, particularly in Tantric philosophy, described the embryonic Universe as a bindu (a point), which contained the totality of the energy and form of being (the goddess Shakti), intertwined with pure consciousness (her consort, Shiva, also both creator and destroyer). From this arose the primordial vibration, om (equivalent to Brahman or the Tao), that gave rise to the world we perceive.

Impossible though it may be to comprehend the nameless underlying oneness - whether from a scientific or religious perspective - and to escape from the illusory world (maya) to which our senses confine us, mystics can experience the unity of being through meditation, whilst scientists can create maps (largely in the form of mathematical equations) that provide guides to the pathways of being and non-being. One such mathematical map, S-matrix theory (which concerns hadrons, such as protons and neutrons), states that interactions between particles follow certain rules that determine the energy levels at which the probability of one or several particles emerging, disappearing, or transforming into other particles, dramatically increases. Such enhanced probabilities have been termed “resonances” in analogy with the optimal frequencies at which sound waves are transmitted in bounded spaces. Resonances, or energy channels (familiar to Eastern philosophers), must surely influence the macroscopic world that we perceive. Cancer, for example, occurs when and where the set of factors that govern its emergence achieve maximal complementary. And although seemingly unrelated to the esoterica of particle physics, cancer is the end result of a series of genetic changes brought about by the interactions of molecules and their constituent atoms, the pathways of which are ultimately defined by the mathematics of quantum mechanics.

Probability Pathways in Carcinogenesis

We often speak of the genetic and environmental determinants of cancer, but this language is misleading, for such factors do not act independently, but are part of the interpenetrating web referred to by both Eastern philosophers and quantum physicists. The environment, through a process of Darwinian evolution, molds the genome of living creatures, and is, in turn, affected by their actions (particularly those of humans). Carcinogens do not cause cancer, but rather interact with a myriad of other factors to create “resonant” frequencies in time and place, i.e., they significantly increase the probability that cancer will occur. Carcinogens in tobacco smoke, for example, are capable of greatly influencing the probability of cancer, but whether a particular smoker develops a particular cancer depends upon the age at which smoking began, the duration and intensity of smoking, exposure to other environmental pollutants, and in some cases dietary and/or hormonal factors. It also depends upon the particular set of relevant genetic alleles (i.e., very slightly different versions of the same gene) inherited by the smoker. Such alleles include genes relevant to behavior and physical dependence on nicotine, the absorption and processing of the carcinogens in tobacco smoke, the ability of cells to prevent or repair the damage caused, and the inherent likelihood of mistakes arising or persisting in the course of gene replication (during cell division), which may, in some cases, be a major contributor to the cancer “probability wave.” Which alleles are inherited will depend upon the genetic constitution of the smoker's ancestors, itself molded by the selective effect of the environment(s) in which they lived. We cannot possibly know all of these variables for all cancers, but we can recognize particularly potent predisposing factors for some cancers, and develop strategies to modify their influence (Figure 1).

Figure 1. A simplified version of the web of cancer probability. Each factor (which may be composite) as well as many factors not shown and others yet to be identified contributes to the overall probability of cancer. The relative weight of each factor varies from one individual to another and from one cancer to another.

Changing Cancer Resonances

It is, of course, impossible to have any clear idea of the incidence of cancer in paleolithic populations although both the incidence and spectrum of cancers must have differed greatly from the patterns observed today - even in modern aboriginal peoples. Once exposed to technically advanced societies, however, aboriginals usually give up their traditional lifestyles and tend to succumb to unhealthy behaviors such as smoking and heavy alcohol consumption, contributing to their high premature mortality rates. In the Pima “Indians” of Arizona, genetic selection over many centuries of those best able to survive the adverse circumstances of their traditional lifestyle has led to a strong susceptibility to obesity and its consequences, including type II diabetes (present in 50% of the tribe between the ages of 30 and 64 years), hypertension, gall stones, and gall bladder and bile duct cancers. This example vividly demonstrates how genetic and environmental factors interact, and how beneficial genetic traits in one set of circumstances may be deleterious in another. Other diseases may be transmitted by direct contacts with new populations. In Quechua Indians, descendants of the Incas, the commonest cancer is cervical cancer, but a study of Human Papilloma Virus (HPV) subtypes known to be strongly associated with this disease has shown the majority to be of European origin.

Unlike their modern relatives, ancient hunter-gatherer populations probably had an extremely low incidence of cancer. Peto and Doll have proposed that approximately one third of cancer risk in affluent societies is related to tobacco, a third to diet, and perhaps a sixth to chronic infectious diseases. The remainder stems from a miscellany of factors, including prolonged exposure to physical or chemical agents - all subject to the inherited ability to maintain the integrity of the genome. Apart from sunlight and infectious diseases, most environmental factors relevant to cancer today did not apply to hunter-gatherer peoples in their natural state. Pre-industrial farming communities were at risk for additional infectious diseases, in part because of increased population density, but also because of their close proximity to animal and human waste - excrement was used as fertilizer, building material and fuel. It is highly probable that the majority of their cancer risk was attributable to infections, although factors such as indoor pollution (e.g., from open fires) and dietary habits doubtless played some role. A number of chronic diseases caused by bacteria, viruses and parasitic flatworms (flukes) are known to be important risk factors in the development of certain human cancers, including stomach (Helicobacteri pylori) liver (hepatitis B and C, and Clonorchis sinensis), bladder (Schistosoma hematobium) and intestinal cancer (Schistosoma mansoni). The need to locate agricultural communities close to water, and the use of irrigation canals to extend arable land increased the risk of infestation by flukes, whose transmission requires water snails and sometimes fish as intermediate hosts. The frequency of sexually transmitted diseases probably also differed markedly across the span of history, and the prevalence of HPV doubtless increased as societies became larger and more inhomogeneous, thereby lessening the influence of culturally-determined restrictions on sexual relations - a process hastened, no doubt, by coordinated military expeditions associated with routine violation or enslavement of female populations. HIV/AIDS is an example of a recently emerged sexually transmitted infection associated with an increased risk of cancer. Interestingly, fertility rates may also influence cancer risk. The incidence of breast cancer, a hormone-dependent disease, for example, has increased in parallel to the decreased size of families and much more limited breast feeding in the affluent populations that emerged after the technological revolution.

Figure 2. Crude (actual) annual incidence and mortality rates per 100,000 of cancer in WHO world regions. Data from Globocan 2002.

Figure 3. Age-standardized (to a world population structure) annual incidence and mortality rates of cancer per 100,000 in WHO world regions. Data from Globocan 2002. Age standardized rates are used for comparative purposes, but show (compare with figure 1) how overall rates increase when populations age. Age intensifies many factors, e.g., environmental exposures, but sometimes, e.g., in pediatric cancers, its effect derives from age-related physiological differences.

WU-WEI (NON-ACTION) AND CANCER CONTROL Avoid smoking; avoid excessive alcohol consumption; avoid high fat diets; avoid excessive exposure to potentially harmful environmental agents.

Cancer then, like major warfare, global epidemics, poverty and environmental damage, can largely be considered an unwanted potentially avoidable effect of socioeconomic development. Not surprisingly, marked regional variations in the global cancer pattern exist, reflecting differences in socioeconomic development, lifestyles and the pattern of relevant infections - influenced to a greater or lesser degree by the intrusion of the unhealthy attributes of industrialization, particularly smoking. Unfortunately, more limited industrialization is often associated with more limited protection against exposure to industrial and agricultural chemicals, so that associated health hazards can be more, not less. Cancer, however, has a relatively low incidence in many developing countries (Figures 2 and 3), particularly those in which the smoking epidemic is still in its early phases (Figure 4) and caloric intake is low. Thus, in many of the poorer countries, there is an opportunity to pre-empt some part of the expected rise in cancer, i.e., to introduce prevention policies before anticipated increases in risk factors, such as smoking, amplified by aging of the population, dominate the cancer pattern.

Figure 4. Cigarette consumption in selected countries. *Indicates countries in which consumption is declining. Data from The Tobacco Atlas, WHO, 2004 (available on-line).

It is one of the tragedies of socioeconomic development that even when the factors that increase the incidence of specific diseases, such as cancer, are recognized, economic considerations (that may benefit only a small sector of society) lead to attempts to inhibit appropriate countermeasures, or even to promote unhealthy behaviors. Such actions are clearly antisocial, but are difficult to oppose without strong support from international governmental and non-governmental organizations. In an era also faced by the twin dangers of nuclear proliferation and major environmental degradation it is difficult to discount, lightly, the possibility of an approaching Armageddon. Yet the Nobel prize in physics this year was awarded for the discovery of asymptotic freedom, whereby the strong nuclear force that binds the quarks within atomic nuclei increases as they move further apart - explaining why quarks have more freedom when close together, and why they cannot exist as individual particles.

This step towards the physicists’ dream of a unified theory of space-time, energy and matter could also be a description of an ideal human society and its relationship to the interconnected cosmic web. Perhaps quantum physics will finally help us to understand what it is that the Tikigagmiut feel when they look in the direction of the pointing finger that is Tikigaq.

Part 2 - The Lives of Cells - will follow in the next newsletter.