Disease Selection

The Way Disease Changed the World

Roger Webber

• Publisher: CAB International
• Year: 2015
• Print ISBN: 9781780646831
• eBook ISBN: 9781780646855
• Topic: Medicina
• Subtopic: Malattie infettive

Diseases have had more influence on us than we realize. They have taken a major role in making us humans and probably determine the way we run our lives. They emerged with us from our ancestral home in Africa, to spread to the rest of the planet. History is full of the great epidemics of plague, smallpox and anthrax, with the present catastrophe of HIV that is changing the demography of the world in a similar way to its predecessors. We survived because of our genetic variation and immune system and it will be this that will save us again.So fundamental has been the part that disease has played in the world that it has brought about change, just as much as has natural selection. Actually disease has been another force, sometimes acting with natural selection but often in opposition. It continues to have a far more profound effect on all of us than realized, selecting the course of the world just as much as nature has.

The Sexual Revolution1

Origin of Life

The general consensus is that life originated in the oceans some 4 billion years before present from the heat and nutrients of hydrothermal vents. Although the heat originated from volcanic processes and was intense, it was cooled by the surrounding ocean and a gradient of temperature was created that provided the ideal conditions for life to start. This first life was very simple, just a cell wall containing cytoplasm, and could quite easily have happened, as shown by Wagner in his book Arrival of the Fittest; it was termed a prokaryote.

All cell walls are made from amphiphilic lipids, which are so called because one end likes water and the other likes oils and not water. This property enables lipid molecules to be directionally arranged, a phenomenon that is seen if a thin film of oil is spread on to water, in which it naturally forms into globules, thereby separating the oily components from the water outside. This is thought to be how simple cell walls originated, to be subsequently improved upon by random mutations of their organic contents.

These mechanisms enabled the development of two early life forms, the Archaea and the Bacteria, which set about colonizing the planet. Bacteria are found on all surfaces and in every part of the earth, even within rocks and thermal springs that are too hot for any other form of life. They have been found as far as 5.3 km down a borehole in Sweden, and in hydrothermal vents where they survive on sulfate and hydrogen, while one species known as Deinococcus radiodurans is able, as its name implies, to survive high doses of ionizing radiation, as well as being dried out and subjected to intense ultraviolet light.

Our bodies are covered with bacteria, they are in every orifice and happily live within our intestines (Fig. 1.1), providing us with almost 15% of extra calories from our food. Bacteria were so successful and in such abundance that for several millennia they and the Archaea were the only forms of life on our planet, and there seemed no need for there to be any other. They were modified and became adapted to every place within our world (and possibly in other worlds). Yet, despite this abundance and variety, they reproduce in the simplest of ways – by dividing in half – in a process that is known as binary fission or asexual reproduction. (There are exceptions, with some bacteria using a modified form of sexual reproduction, but this only happens under certain conditions and in a minority of cases.)

Fig. 1.1. A highly magnified picture of bacteria in the human intestines. (Reproduced with permission from Bluecrayola.)

Binary fission is a very easy process. First, a copy is made of the genetic material (chromosomal DNA), then the cytoplasm and cell wall divide, so that two identical organisms are produced. While this mechanism might seem applicable only to single-celled organisms, even multicellular life forms such as hydra can reproduce in the same way. Indeed, one might ask why, if reproduction can be achieved so simply, did animals develop two sexes and go through a complicated procedure to reproduce themselves? – a topic that is discussed below. Even in higher animals though, there is still a surprising amount of symmetry within the body plan – two forelimbs, two hindlimbs, paired lungs and paired kidneys; and the heart has four chambers, one pair for receiving the blood and another for driving it round the body, which originally served each side of the body, but developed in mammals into a venous and arterial system for the whole body. It is almost as though the body could still be divided down the middle and each half then grow opposite parts.

Bacteria are far more efficient at reproduction than higher animals, not only in simplicity but also in rapidity, so that within a short space of time, favourable conditions allow the production of millions of them. However, it is this very success that is their weakest point because they are all identical. If there is something that can kill just one of them, then providing there is sufficient of that substance, it will kill all of them. When an advert claims that its product will kill 99.9% of germs it is probably correct.

None the less, random mutations do occur, so that in time a resistant strain could develop to the killer substance, and as every bacterium in that batch will be identical, all will have the same capacity of resistance. It is the rapidity with which bacteria reproduce that increases the chance of a beneficial mutation occurring. A single bacterium will produce a mutation at a rate of 10⁴–10⁹ cell divisions and if one of these should have an advantage, it will be selected and so become the predominant type. But if another lethal substance is used, all of the bacteria will once more be killed in an all or nothing process, there are not even a few that will survive to be the parents of a fitter strain. This is where sexually reproducing organisms have an advantage.

Animals with two sexes mix the genetic material from each parent so that there are numerous possible outcomes. Some individuals will be inherently weak and not survive to adulthood, while others will have a more suitable genetic make-up that enables them to be strong enough to survive and reproduce themselves. Some will have certain characteristics and abilities to withstand adverse environments while others will not. It was this necessity to survive the challenge from disease-producing organisms that led to the evolutionary selection of sexual reproduction. We are two sexes because we are more able to cope with disease that way. (This is a simplification of the original work done by Bill Hamilton, which is well described by Matt Ridley in The Red Queen.)

This challenge from disease came surprisingly early in life, with bacteria not only preying on each other but the mechanism of parasitism also appearing to have developed right from when life first started. Either one bacterium would invade another and live off its cell contents to the detriment of its host or it would be inadvertently engulfed, in the manner that an amoeba engulfs a foreign body, but not destroyed. From this position within the host cell, and providing that it survived, the bacterium could exploit the host cell to its advantage.

Viruses are incomplete life forms, needing the contents of a cellular organism to develop and reproduce, and they too have been found to have been present at the very early stages of life. Indeed, they might have been early attempts at creating life that were not able to complete the process. Every bacterium has a virus that preys on it, so the origin of disease, whether it be bacterial or viral, has been with us right from the very start of life.

It was this process of invasion of another bacterium, or that of being engulfed by one, that led to the most momentous development in life – the development of the eukaryotic cell. This is a more complex cell form than a prokaryotic cell, and contains a nucleus and other organelles; it is the basis of all multicellular organisms, both plant and animal.

The development of the eukaryotic cell was probably driven by attempts to develop new energy sources, particularly photosynthesis, that would free an organism from its dependence on chemical energy. But one of the consequences was the production of oxygen, which was like a poison to anaerobic bacteria. This not only changed the dominance of existing species but presented a continuing battle that is still with us today – how to prevent an excess of oxidants from building up in tissues. This topic will be covered in more detail in Chapters 15 and 16.

Evolutionary biologists have looked for some time for a suitable prokaryotic cell that when engulfed by another would form the nucleus of the nascent eukaryotic cell, but none has been identified that matches all the required criteria. However, Luis Villarreal, working with viruses, has come to the astounding conclusion that the primitive cell nucleus could have originated from a complex virus. The vaccinia virus, for example, seems to have all the same mechanisms that are required by a eukaryotic cell nucleus. The virus that formed the nucleus brought with it all the basic genes – thought to number about 324 – that are necessary to form the cell.

It requires a little time, and perhaps rereading of what has just been said, to realize that every cell in our bodies has a nucleus that was derived from a virus. We are the result of a very early disease process!

If this takes some getting used to, a fact of even more astonishment, and more generally agreed, is that some of the cellular organelles, particularly the mitochondria, could have been derived from parasitic bacteria. In the game of fleeing from threatening viruses, a bacterium might allow itself to be engulfed by another for protection, and if this set-up is sufficiently stable, then a symbiotic relationship will result. This is thought to have happened with a bacterium that subsequently became the powerhouse of all cells, the mitochondria.

One of the reasons we know that this happened is that mitochondria contain their own DNA, which means that the genetic make-up of mitochondria can be examined and compared with that of different bacteria to determine its close relatives. Drs Wang and Wu from the University of Virginia have just done this and come to the surprising finding that the inclusion bacteria (mitochondria) are more closely related to a parasitic ancestor that stole energy from its host, rather than giving it. They examined the pre-mitochondria (the earliest form and last common ancestor of currently existing mitochondria) and were able to predict that these possessed a plastid/parasite type ATP/ADP translocase that imported ATP from the host, so they were actually energy parasites. In addition the pre-mitochondria had a large number of flagellar genes, suggesting that the ancestor bacterium was likely to have been motile, and capable of oxidative phosphorylation under low oxygen conditions.

So not only is the nucleus of our cells derived from a virus but the mitochondria are from a parasitic bacterium. There can be no closer link between us and disease-producing organisms.

Coming back to the original discussion on sexual reproduction, this finding also helps to explain why there is such a disparity between the egg and sperm in human reproduction. Only the egg contains mitochondria, the sperm has just nuclear chromosomal (genetic) material and a flagellar mechanism that breaks off when the successful sperm enters the egg to fertilize it. The mitochondria were removed from the germinal cell that developed into a sperm, and there is no place for any other potentially pathogenic material to infect the egg during this conjugation. There is always the danger that the original bacteria, especially if there were two of them (one from the male and one from the female), could become pathogenic once more, so by removing the one from the male gamete this reversion is unlikely to take place. The cell is taking no risk that the early battle between the pre-eukaryotic cell and the invading bacteria should need to be fought again.

Complex Life

The invention of the eukaryotic cell took place about 2.2 to 1.8 billion years before present, and enabled the development of more complex life forms. There was then a period of over a billion years during which little happened, which led to one of the most dynamic periods in the development of life, the Cambrian explosion, some 542 million years ago. This is so called because of the profusion of new life forms that occurred over a brief period of time, although present-day thinking suggests that these developments might actually have occurred over a longer time scale. Early complex life forms were probably soft bodied and so left no imprint on the fossil record; it was not until the appearance of animals with external skeletons that we find fossil remains. The first of these to be found were the trilobites in the 1840s, but wider searches discovered stromatolites dating back to at least 1.4 billion years before present. These consist of algal mats related to green algae, and are significant because of their production of oxygen, which helped to provide the level of this gas in the atmosphere that we breathe today. Stromatolites can still be found in the shallow waters of Shark Bay in Western Australia.

This profusion of life led to the origins of many of the phyla which, apart from the bacteria and viruses, include all other forms of life that took on a parasitic type of existence and became the disease organisms that trouble us today. One of the earliest kingdoms to emerge included Trichomonas and Giardia, two important parasites of humans. Other relatively early parasites include Plasmodium, Leishmania and Trypanosoma, some of the most important of all disease-producing organisms.

These organisms not only exploited every niche of their environment but also found ways to live off the more complex animals that subsequently developed. This could either be to the advantage of the animal, as in the case of gut bacteria, which assist in breaking down food so that it can be digested, or to its disadvantage, as in the development of disease.

Natural History of Disease

When a new disease develops (from a random mutation or by transfer from another species) its effect on the animal it attacks will be severe. The animal has never met the organism before so it has never had an opportunity to develop defensive mechanisms and will either be killed or have a severe reaction. Such was the effect that the completely new disease severe acute respiratory syndrome (SARS) had on the first unfortunate human beings to meet this virus; out of the 8422 cases, there were 916 deaths and a number of survivors suffered chronic lung damage. If we had reproduced asexually like bacteria, then there would have been no survivors from those that had been infected, but because of the different genetic make-up of individuals, there were some that overcame the disease. One could hypothesize that if the disease had been allowed to run its course, then proportionally more people would have survived as they inherited defence mechanisms that made them more able to tolerate the organism. Fortunately, a major effort was made to eradicate SARS before it became a universal problem, but there are many other diseases that were not eradicated, with tuberculosis and leprosy being good examples of the natural progression of a disease.

Tuberculosis (TB) was one of the major killers of 19th century Europe, where it was known as consumption. This is in fact a very good description of the disease, as it gradually consumes the person who has it, the main clinical criteria being loss of weight and anaemia. As TB is predominantly a respiratory infection there is a persistent cough, often accompanied by the distressing symptom of coughing up blood, or haemoptysis. The infected person gradually wastes away, and generally has a long, lingering death.

Consumption spared nobody, wealth or ability being no barrier, and one of the most tragic examples was that of the famous literary family, the Brontës. Patrick and Maria Branwell Brontë had six children, among them the famous novelists Charlotte and Emily. The first to die of consumption was the mother, Maria Branwell, and the two eldest children, Maria and Elizabeth, in 1821. The son, Patrick Branwell (fuelled by his addiction to opium and alcohol), expired in September and Emily in December 1848, a year after the publication of her famous novel Wuthering Heights. Emily’s youngest sister, Anne, died in 18...

Table of contents

• Cover
• Half Title
• Dedication
• Title
• Copyright
• Contents
• List of Illustrations
• Preface and Acknowledgements
• Introduction
• 1 The Sexual Revolution
• 2 Out of Africa
• 3 Host/Parasite Interaction
• 4 Using a Vector
• 5 The Great Plagues
• 6 Missionaries of Death
• 7 The Slave Trade in Parasites
• 8 Eden’s Garden of South America
• 9 A Glass of Water
• 10 The Great War
• 11 Man’s Best Friend?
• 12 The Animal Connection
• 13 Not Clean
• 14 Too Clean
• 15 The Food We Eat
• 16 Cancer
• 17 Climate Change and Population Movements
• 18 Disappeared and Emergent Diseases
• 19 The Future
• 20 Conclusions
• Resource Material and Suggested Further Reading
• Index
• About the Author
• Back Cover