The Community and Cancer

Part 1. Cooperation and Competition

by Ian Magrath

How selfish soever man may be supposed, there are evidently some principles in his nature, which interest him in the fortunes of others, and render their happiness necessary to him, though he derives nothing from it, except the pleasure of seeing it. Adam Smith. The Theory of Moral Sentiments.

Example of a fossil of an Ediacaran animal from the Precambrian era. This one is called Dickinsonia costata. Its relationship with modern animals is speculative; it has been variously considered an annelid worm or a cnidarian (a group including jelly-fish, corals and sea anemones). Courtesy of UC Museum of Paleonthology, www.ucmp.berkeley.edu

A brief survey of the events that have occurred in the 15 billion years or so that the universe has existed gives the impression of an inevitable progression towards the emergence of life, and ultimately of intelligent beings. The sense of inevitability arises, in part, from the particular values of the physical constants - values that have permitted the creation of atoms and molecules of continuously increasing complexity since hydrogen emerged at the time of the Big Bang. Statistical considerations also favor inevitability, since even if the formation of planets able to support life were an exceedingly unlikely event, the passage of billions of years and the creation of trillions of planetary systems in the hundreds of billions of galaxies known to exist would seem to guarantee the creation of life and the eventual development of rational thought at least once in the universe, and possibly innumerable times. Inevitability may, of course, be an illusion, arising from our particular vantage point as recently evolved intelligent beings - prior evolutionary steps, of necessity, lead to Homo sapiens. But whether the evolution of intelligence was inevitable or not, our perspective is unavoidably anthropocentric and presumes, at least in non-scientific circles, that Homo sapiens is the culmination of the evolutionary process. The corresponding social implications have been dire, for such a view fosters the idea that nature exists purely to be gainfully exploited, justifying the mutilation and pollution of the very source of our being. Ancient ecosystems such as tropical rain forests - vast repositories of information and products of great potential value (see Table) that have barely begun to be categorized - have already been decimated. Apart from the effect on biodiversity, the loss of trees (at the rate of 25 million acres a year) reduces the consumption of carbon dioxide by photosynthesis, contributing significantly to global warming.

Within human society a parallel trend exists whereby the few rich and powerful assume their interests to be paramount, while the voices of the numerous poor are scarcely heard. Hobsbawm, in The Age of Extremes, speaks of the social changes in the 1960s as being “best understood as the triumph of the individual over society, or rather, the breaking of the threads which in the past had woven human beings into social textures.” This comment goes a long way towards explaining the root cause of the present enormous inequality in the world, which greatly exacerbates social tensions. While poverty is a major cause of malnutrition and ill-health, as well as poor access to health care in the developing countries, over-consumption in the high-income countries, particularly in the USA and UK, has created an epidemic of obesity, diabetes and associated diseases, including various cancers. The role of tobacco in the causation of many diseases, including cancer, has been known for decades, but governments have failed to address the problem with any real enthusiasm, largely due to commercial interests, or, particularly in developing countries, because of an urgent need of money. The Global Tobacco Framework is a major achievement, but why did it take so long to accomplish, and will a majority of member states heed its exhortations? The Wealth of Nations consists of three components - material, cultural and biological. At the present time, it would seem, the latter two are being sacrificed in favor of the former, while the distribution of material wealth is grossly uneven. The value of reason, it would seem, depends upon the uses to which it is put.

Product Purpose   Origin   Digitalis    Cardiostimulant    Digitalis purpurea (foxglove)   Atropine   Anticholinergic   Atropa belladonna (deadly nightshade)   Camptothecin   Anti-cancer   Camptotheca acuminata   L-dopa   Anti-Parkinsonism   Mucuna species (e.g., velvetbean)   Ephedrine   Sympathomimetic   Ephedra sinica   Etoposide   Anti-cancer   Podophyllum poltata (mayapple)   Irinotecan   Anti-cancer   Camtotheca acuminata   Morphine   Analgesic   Papava somnifera (poppy)   Pilocarpine   Sympathomimetic   Pilocarpus jaborandi (Indian hemp)   Taxol   Anti-cancer   Taxis brevifolia (Pacific yew)   Teniposide   Anti-cancer   Podophyllum peltatum (mayapple)   Topotecan   Anti-cancer   Camptotheca acuminata   Tubocurarine   Muscle relaxant   Chondodendrum tomentosum   Vinblastine   Anti-cancer   Cantharanthus roseus (periwinkle)   Vincristine   Anti-cancer   Cantharanthus roseus (periwinkle)   Cyclosporine   Immunosuppressive   Hypocladium inflatum   Tacrolimus   Immunosuppressive   Tolyplocadium inflatum   Lovostatin   Cholesterol lowering   Monascus purpuris (red yeast rice)   Penicillin   Antibiotic   Penicillin notatum   Amimnoglycosides   Antibiotics   Streptomyces species   Beta-lactams   Antibiotics   Streptomyces species   Fluoroquinolones   Antibiotics   Streptomyces species   Bleomycin   Anti-cancer   Streptomyces verticillis

Table: Some Medicinal Products Derived from Plants (top panel), Fungi (middle panel) and Bacteria (lower panel).

The Record of Reason

Homo sapiens is one of the most recent species to emerge and, at least in terms of his faculty for rational thought and tool making, would appear to be the most complex animal ever to have evolved. But complexity does not necessarily equate with success and on its present record, rational thought is unlikely to greatly benefit life on Earth. Even from the perspective of mankind alone, the remarkable technological progress of recent years has failed to prevent the lives of at least half, and probably the majority of humans on the planet, from continuing to meet Thomas Hobbes' description, in 1651, of being “solitary, poor, nasty, brutish and short.” It is of some interest, even if tongue-in-cheek, to compare the contributions to life of our distant ancestors, the prokaryotes, with our own. In the course of some three billion years these simple cells created the basic metabolic pathways used by all life forms, an oxygen-containing atmosphere and eukaryotic cells, all essential to the emergence of multicellular organisms. This led to the explosion of animal biodiversity in the Cambrian period, beginning just over 500 million years ago, and the colonization of the land by animals and plants. In contrast, human activities have, in the space of a perhaps a few thousand years and with dramatic acceleration in the last fifty, destroyed large swathes of primordial forest, created massive pollution, and initiated the sixth major extinction of species that has occurred since the Cambrian explosion. Human activities are also bringing about significant climate change, which threatens to create a major global catastrophe. Intelligence, it would seem, has yet to overcome instinctive behavior; indeed, its preponderant use, at least, in political arenas, would appear to be the justification of behavior that evolved in the context of survival in the prehistoric era, and which has become horribly distorted by the very success of humans in terms of population growth and the development of ever more effective tools and weapons. As the human population continues to expand, accompanied by an increasing demand for energy and food, it is imperative that people see themselves not as distinct from the planetary ecosystem, but as part of it, and with a unique and unprecedented responsibility towards it that stems directly from their ability to appreciate its magical beauty, its complex interrelationships, its miraculous mechanisms and its profound mystery.

Oekos

The sense of unity with respect to the ecosystem (Greek, oekos; house) we are part of probably existed in prehistoric human communities to a much greater extent than it does today. Yet scientific evidence points strongly towards a singular origin of the trinity of energy, matter and life. The long journey from the perfect point, that was the beginning of the universe, to the human brain has occurred in a series of steps, each dependent on the one before. Sometimes, dramatic changes have occurred in minuscule fractions of a second (e.g., the events that occurred immediately after the Big Bang, relating to primordial energy fields and particles) while others have taken billions of years of preparation (e.g., the creation of the 92 elements in massive stars). The shallow seas, that filled much of the surface of the planet Earth as soon as it had cooled sufficiently, must have provided an appropriate environment for the emergence of life, for fossilized stromalites, the remains of huge mattresses (Greek, stroma) of prokaryotic cells, date back to less than a billion years after the formation of Earth. Similar domed structures containing living microorganisms continue to form today. The fact that all living organisms, including humans, use the same molecular information systems and basic metabolic pathways confirms life’s unique origin - the biological equivalent of the cosmic singularity. If there were once other life forms, they have certainly left no trace.

This puts a very different gloss on what we, from our individualistic viewpoints, see as competition - a lesson translatable from ecology to economics. Prior to multicellular organisms, individual cells generally had an extremely transient existence, dividing over and over again to give rise to vast clones of cells. Here, the species (a much less well-defined concept in prokaryotes) rather than the individual cell is automatically conceived of as the biological entity. Darwin’s theory of “survival of the fittest” refers to a process whereby a species becomes increasingly adapted to survival in a particular ecological niche through natural selection of the most appropriate genetic traits from among the wide range expressed in the individuals of the species. Over time, the higher reproductive rate of the “fittest” individuals ensures that their genes come to predominate in the population. Horizontal transfer of genes in prokaryotes, which even occurs between species, permits this process to be greatly speeded up. Darwin, of course, was unaware of the existence of bacteria, and his theory was derived from the study of animals and plants, where natural selection is not only a process of adaptation to a particular habitat, and to dispersal to other habitats (adaptive radiation), but also has much to do with the establishment of a harmonious relationship among the various species (i.e., reproductively isolated populations) living in a particular habitat. Such a balance, although it involves predation, can be seen primarily as a cooperative process that ensures maximal use of available resources through maximization of biodiversity, a process in which prokaryotes continue to play a vital role. In more complex species, remarkable degrees of specialization occur; but species also share each other’s captured energy as well as essential molecules. These intimate forms of cooperation in multicellular organisms are not dissimilar, in principle, to gene transfer in prokaryotes. In stable ecosystems both the number of species and the numbers of individuals in each species remain within defined limits over relatively long periods of time, varying according to the size and type of habitat.

Terrestrial Colonization - A Joint Venture

Animals and plants emerged on Earth in the course of the last billion years. This new phase of evolution was eventually to lead to the remarkable ability of life to contemplate itself. The best preserved of the earliest animal fossils (marine) were discovered in the Ediacara Hills of Australia by a geologist, Reginald Spriggs, in 1946. The classification of the Ediacaran animals, which lived between 540 and 650 million years ago, is difficult, and while some resemble modern phyla, such as the annelid worms, arthropods of various kinds (insects and crustaceans), or corals, others may belong to phyla long since extinct. The colonization of the land by animals, plants and fungi probably began somewhat more than 400 million years ago. One element vital for plant evolution, among many others, was the creation of soil. This was provided by decaying organic matter (courtesy of prokaryotes), mixed with rock particles and tilled by the earliest animals, such as those resembling annelid worms and insects. Similar organisms continue to perform this important task today. More complex terrestrial plants and animals had to await both the development of the more efficient energy generation of aerobic respiration, and also sufficiently high atmospheric oxygen levels. The presence of an ozone layer, also dependent upon high atmospheric oxygen concentrations, was necessary to protect against harsh ultraviolet light. Unfortunately, the fruits of billions of years of photosynthesis could be destroyed in a few decades; loss of the ozone layer would have a profound effect on a broad range of terrestrial life forms. Even the present degree of depletion, caused by atmospheric pollution by humans, has led to an increase in the incidence of a common skin cancer - melanoma - as well as other skin and eye diseases. Increased UV radiation is also likely to decrease populations of marine organisms, including phytoplankton, which will have a corresponding effect on fish, with negative effects on the human food chain.

Ultimate success in terms of the invasion of land was dependent upon many other forms of close cooperation, which also persist to the present day. Of particular importance was the symbiotic relationship between plants and fungi, which first occurred in the form of lichens, most probably one of the earliest terrestrial immigrants. Heinrich Anton de Barry, who coined the word symbiosis in 1866, showed that lichens are not single organisms, but result from the close cooperation between an autotroph (organisms able to trap energy from the sun or inorganic materials) and a heterotroph (life forms that feed on other life forms). Since fungi are able to absorb large quantities of water and to extract minerals from particles of rock, they can protect the sensitive algae from dessication and provide them with minerals in return for a share in the carbohydrates produced by the algae (during photosynthesis). Lichens remain among the first organisms to colonize forbidding environments, such as deserts, but as fungi and plants evolved, the symbiotic relationship between them also developed. Today, mycorrhizal fungi are closely associated with the roots of nearly all plants, continuing to assist in the absorption of minerals and water and uniting with them in a vast cooperative, if underground, network. Some relationships are not precisely balanced, and sometimes fungi kill the trees they would otherwise succor. Life, like human society, is, however, a work in progress, and parasites, who generally take more than they give, abound at all levels. They even have their own parasites (hyperparasites).

Prokaryotes continue to be vital to the survival of more complex organisms on land. Nitrogen-fixing bacteria live in rhizobial nodules on the roots of some plants, giving them access to this abundant atmospheric element, which is essential to the synthesis of a number of vital molecules, including amino acids, the building blocks of proteins. A particularly important collaboration is that between flowering plants (angiosperms) and insects, birds and mammals. Such plants (which include many trees) like other life forms, provide an immense variety of habitats and food for animals - conveniently signposted by the brilliant colors of flowers, or the smell of fruits. Insects, in return, intercede in the process of plant reproduction (pollination) and to a lesser extent, dispersal, while birds and animals have a major role in spreading seeds, either through ingestion, or carriage on some part of their body. This willingness to “pay,” as it were, a price in energy for the benefit of the species is not limited to plants. Animals prey upon each other, creating balanced relationships which permit the species of both predator and prey to survive. Disturbance of this balance, which may have taken millions of years to establish, via the introduction of alien species or the removal of a particular predator - both of which are often the result of human colonization - can result in multiple extinctions and a marked reduction in biodiversity.

Lambornella clarki

A remarkable demonstration of the cooperative nature of predation is found in the relationship between the single-celled ciliate, Lambornella clarki, and the mosquito, Aedes sierrensis. Lambornella lives in rain-filled tree holes in the western United States, where the mosquito lays its eggs. Both ciliates and mosquito larvae are able to prey on bacteria in the water, but the mosquito larvae also feed on Lambornella, if present. In this case chemicals released by the larvae trigger a morphological change in Lambornella (similar to that occurring in other Tetrahymena ciliates), such that it can penetrate the tissues and feed on the flesh of some of the mosquito larvae. Infested larvae are still able to develop into adults, in which the parasitic ciliates preferentially migrate to the ovaries, rendering the mosquito sterile and also triggering hyperactive egg-laying behavior. The mosquito, loaded with ciliates, flies to other holes, and, in the process of trying to lay eggs, or through dying on the surface of the water, deposits Lambornella into the water, thus ensuring its dispersal.

The story does not end there. The female of Aedes sierrensis feeds avidly on the blood of large mammals, including humans, and is the vector of the parasitic microfilarial worm which causes heart-worm disease in dogs. It is also capable of transmitting Western Equine Encephalitis virus to people and horses. There are many variations on this dance of nature. Some Tetrahymena are exclusively free-living; others are exclusively parasitic, e.g., on fish, or, in the case of Plasmodium species, which cause malaria, on humans. In this case, Anopheline mosquitoes rather than Aedes play a critical role in the dispersal of the ciliate. Malaria kills over a million people each year, and may be a factor in the high incidence of a common childhood cancer in equatorial Africa - Burkitt lymphoma. From the biological perspective, human infectious and parasitic diseases represent a means of maintaining the human population size within the limits specified by the natural ecosystem. People, of course, see things differently, and the present population explosion occurring in developing countries is, in large part, a consequence of the conquest of infectious diseases and the development of much more efficient methods of food production. Reason alone might suggest that the substitution of birth control for the regulation of the population size through disease would help to reduce the ecological damage presently caused by humans, but the issue is complicated by the need for education, by cost, even if small, and by cultural and religious ideologies.

"It is the highest impertinence and presumption, in kings and ministers to pretend to watch over the economy of private people, and to restrain their expense... They are themselves always, and without exception, the greatest spendthrifts in the society." Adam Smith, The Wealth of Nations

Conflict

Conflict can be seen as a quite different phenomenon from predation, relating more to competition for females within a species (e.g., rutting deer), or dispersal through the establishment and protection of distinct territories occupied by one, or a group of animals. Rarely does conflict of this kind result in death. Territorialism, whether involving competition for physical (relevant to food and energy supplies) or ideological space, is also the ultimate cause of human conflict, but in people, the development of more effective weapons and strategies has led to a significant and ever increasing toll on life as well as a climbing rate of disruption and physical displacement of communities. Rational thought, in other words, appears to enhance rather than diminish conflict. Life’s survival strategy - biodiversity - has been robust enough to overcome five catastrophic extinctions since the emergence of animals and plants. It will probably survive the sixth, a child of rational thought, but whether through the use of reason, or the extinction of intelligent beings, remains to be seen.

Ecology

Human beings, in spite of their modern sense of being apart from nature, represent a generalist species - i.e., one whose strategy is to be reasonably well adapted to a range of habitats rather than highly adapted to a single habitat. Whilst highly adapted species compete more successfully in their particular niche, they also are at higher risk of extinction. Many feather mites, for example, live on particular feathers of particular birds, and their survival depends entirely upon that of their host. Organisms able to live in more than one habitat, particularly if widely dispersed, are more likely to survive natural changes in climate or local ecosystems. Modern humans, although descended from arboreal apes, have colonized a large number of widely dispersed habitats - not through the slow process of structural and behavioral changes on which adaptive radiation depends (although genetic differences do play a role in human adaptation to some environments), but as a consequence of their omnivorous diet, their tool-making skills, their ability to effectively communicate through language and their intelligence. Thus, the species can accumulate collective knowledge and undertake knowledge-based collective action that enhances survival and the quality of life. Knowledge, however, is “context sensitive” and may not always be transferable to different environments and circumstances.

Economy

In the year that the 13 colonies of the United States of America declared their independence from the British Crown (1776), Adam Smith’s book, An Enquiry into the Nature and Causes of The Wealth of Nations, was published. Smith, who is often referred to as the father of economics, was successively professor of logic and of moral philosophy at the University of Glasgow before leaving academic life. His writings encompass a broad range of subjects, including morality and ethics, and he was particularly recognized for his teachings on communication and the importance of sympathy between speaker and listener. This concept spills over into a broader principle encompassing the interactions of societies. In the opening sentences of The Wealth of Nations, Smith pointed out the importance of the division of labor - equivalent, in a community, to biodiversity in an ecosystem. We must be prepared to contribute to society in order to gain something in return. In biological systems, as in human interactions, the contribution can extend to life itself, in which case, the individual surrenders all benefits in favor of the community as a whole. Adams pointed out that societies cannot run on benevolence alone, but he also believed that a system built on greed and selfishness is morally flawed and that an economy without ethics and compassion will be destructive for both individuals and society. In contrast, rewards are found in justice and benevolence. Smith’s well-known metaphor of the invisible hand derived ultimately from the nature of human relationships and, for that matter, of all relationships in which there are communities of living organisms. Where the efforts of individuals are responsible and relate to the needs of the society, society as a whole benefits, but any major departure from this rule will, as Smith observed, result in disaster. Thus, ultimately, the preservation of the community, as does the species, takes precedence over the well-being of individuals.

Ironically, Smith is often quoted in support of a modern notion that profit is the sole purpose of business - leading to the conclusion that commerce has no need to reflect the needs of society. Such forms of business may be characterized at best as social parasitism, at worst, criminal. Health care is a special case since health can be impaired by many commercial products (as well as the manufacturing process itself) while other products are important to its maintenance. The delivery of effective health care is fundamentally related to the well-being of the community and must, therefore, in some way, be regulated at a community level. The free-market model of price determined by demand is seen in this, as in many other contexts, to be naive and unworkable at the level of the patient, since the quality of care requires expert assessment, which the consumer is rarely in a position to undertake. Smith’s emphasis on the need for compassion applies particularly to the provision of health care, but unfortunately, economic considerations affecting only a small sector of society often take precedence over the patient.

A vital question for our times is how to ensure that the ever-increasing knowledge-base can be integrated and used to develop strategies that are ethical, egalitarian, culturally sensitive, lead to respect for and care of the environment and its contained ecosystems, and are based on effective cooperation among macro and micro communities. Any answer to this question must address approaches to diluting nationalistic impulses directed towards dominance and curbing irresponsible or actually harmful business practices. Competition should be used, in analogy with natural selection, to improve the quality of products rather than to maintain, too often through veiled or overt threats, the present unequal distribution of material wealth. International governmental and non-governmental, non-profit organizations (often referred to as Civil Society) will have a particularly important role to play in moving towards this goal which must be achieved if a variety of human ills, including conflict, poverty and disease, are to be overcome.

Part 2. Civil Society, will be published in the next edition of NETWORK.