I am the proud father of a family, one which has grown up and has, indeed, extended our lineage into a new generation. So my own children are encountering a result of the noble estate of parenthood which, to me at least, was quite unexpected. But it will become familiar to them, and to readers who find themselves in a comparable position: it is the amount of junk that accumulates in the house. (I hasten to add, lest one of my grandchildren should read this, that I know it is not junk to them: every celluloid duck, plastic brick, fluffy rabbit, coloured felt-tip, pop record, decayed transistor, pop-art wall poster is known personally to each offspring, complete with history and ownership.) When I was young, toys had a finite, almost predictable lifetime: a clockwork train, for example, would break, be repaired a couple of times, then find its way to a dustbin – within weeks if one was unlucky, in months on an average, in years if one was careful or the toy was particularly good. Today, it seems, toys are indestructible. Bouncer, my forty-four-year-old daughter's brushed nylon washable cuddly-dog is two years younger than its proprietor, having survived for five average lifetimes of the pre-war teddy bear and, albeit a trifle battered, is well set to accompany my granddaughters into adult life. Well, as far as Bouncer and my descendants are concerned, I am happy for all of them; it is the great number of objects of uncertain function, usually fashioned from some kind of plastic, bent, with screws missing, that leaves me with the impression that, in another decade, whole rooms of people's houses will be given over to the storage of beloved toys belonging to beloved offspring!

Nearly thirty years ago I wrote the first edition of Microbes and Man. It was an attempt to introduce educated readers, not necessarily scientists, to the world of microbes, and to survey the impact of these creatures on Mankind's economy and society. The book was a quiet success, I am happy to say: it has been translated into several languages and, because the study of microbes continues to advance in fascinating directions, this is its third major revision.

Microbes have a truly enormous influence on people's lives. They clean up the environment and they make soil fertile; they are allimportant in food technology; they make vitamins within our bodies. They can live peacefully within, around and upon us, and some even protect us from other, harmful, microbes, Yet most people are hardly aware that they exist – until a microbial misfortune happens: perhaps a disease breaks out, some food is spoiled, or some valuable or treasured material is found to have rotted or otherwise deteriorated. Only then do most people remember microbes – so it is hardly surprising that they are widely regarded as nasty; invisible enemies that are to be feared or resented.

In my book I wished to change the microbe's unfortunate public image. Of course, it is true that some microbes, especially certain bacteria and viruses, cause illnesses; of course, too, microbes exist which spoil food and attack non-living material – even damaging such improbable objects as concrete and iron pipes. But most microbes are beneficial. Their value to the food, chemical and pharmaceutical industries is (I hope) well-known to students, and perhaps, since the flowering of genetic engineering, to a minority of laymen.

In the last chapter I looked at the destructive effects that microbes can have on materials. I noted at the start, however, that these destructive effects represent an important function that microbes perform in the natural economy of this planet: they remove the detritus generated by higher plants and animals so as to recirculate the biologically important elements contained in it. Deterioration, corrosion and pollution, when brought about by microbes, are simply special cases of this general function, and so are disposal and cleaningup processes, in which microbes are deliberately used to get rid of unwanted matter and pollutants.

The most important example of a microbiological disposal process is sewage treatment and, since it is fundamental to the health of all civilized societies, as well as being intellectually a most satisfying form of applied microbiology, I shall spend a little time discussing it.

When the population of the world was small, sewage disposal presented few problems. The Greeks and Romans had hygienic systems, often building their baths and lavatories over or near running water. The Romans, in particular, built their baths and sewerage systems to last, and there is a pleasing irony in the fact that these sewerage systems are often all that remain in excavated Roman communities. Standards then fell, and descriptions of life in the Middle Ages and during the Renaissance tell us that human habitations must sometimes have resembled pigsties: steps and odd corners were used as lavatories, refuse was thrown into streets, chamber pots were emptied into the streets and people rarely bathed.

The time has come, I think, to say something of how all these things are known. So often, in books of this kind, the author tells readers the results of scientific progress, paints a sort of panorama of presentday knowledge, without giving them any idea of how this progress came about, of how the knowledge was obtained. This, you may say, is just fine: as a lay reader you are prepared to take my authoritative word that everything written in this book is based on sound, wellconceived experiments.

Would that it were! The trouble with science is that its day-to-day aspects are extremely uncertain. Occasionally great and obvious advances in knowledge take place, but generally research and its applications progress by repetitious and tedious experiments, almost always giving negative or useless results, from which, slowly and over a long period, a picture of the behaviour of whatever-it-is the scientist is studying emerges. No scientific finding is 100 per cent certain; the majority of observations that find application are more than 90 per cent certain. Today, living in a society which depends for its existence on a highly developed technology, it is most important that laymen should be able to view critically the results of scientific research – or at least the claims made for them by journalists, scientists and scientific administrators. It would be very surprising, for example, if some of the information I have written in this book is not falsified by recent research before it is published. How, then, is one to judge what is likely to be well established and what is a little dicey?

I ended the last chapter with a comment hinting at the relationship between pure science and its applications. A clear example is that most personal and important technology, the one called medicine. For medicine is not a science, despite the fact that its practitioners are called doctors. It is a model example of a technology, the application of various branches of science to one facet of the human condition. It is, historically, one of the most admirable examples of science and its application progressing hand-in-hand; even today it is unique among technologies in that a fundamental discovery in, say, a biochemical or physical laboratory may find application in medical practice within weeks instead of years.

The reason is simple to see. We all hate being ill, whether we are doctors, scientists, treasury officials or laymen, and we will support with positive enthusiasm research intended to cure or alleviate this condition, whereas the study of quasars or the ecology of plankton might cause us reservations. Microbiologists have particular cause to be grateful for the self-interest that underlies the relative affluence accorded to medical research because, since microbes are the cause of most illnesses, microbiology has progressed very rapidly in the twentieth century, particularly in its medical aspects. Naturally, this imbalance has left non-medical microbiology in a somewhat neglected state, as will become obvious in later chapters of this book, but though pure microbiologists have at times been critical of the narrowness of their more medical colleagues, this fact should not blind one to the enormous contribution the traditional Path. and Bact. type of scientist has made to the science as a whole.

I imagine that few people are unaware that beers, wines, cheeses and so on are prepared by allowing microbes to act on foodstuffs; even fewer can have failed to recognize that food goes bad through the action of microbes. But these two kinds of microbial activity are relatively minor aspects of the importance of microbes in the whole field of human and animal nutrition. In this chapter I shall naturally deal with food preparation; its spoilage will crop up in Chapter 7. But I shall start with a topic which is quite different, yet which is perhaps the most important stage in nutrition: the assimilation of food.

Assimilation, technically speaking, is the process that follows digestion. Once food is eaten, digestion starts, and enzymes of the mouth, stomach and intestines break the food down into chemical fragments which the organism can absorb into its blood stream and use for its biochemical purposes. Carbohydrates are broken down to sugars, proteins to amino-acids, fats are partly broken down, partly emulsified. Some components of food – woody matter, for instance – are not readily broken down by the digestive enzymes, and it is here that microbes come in. Ruminant mammals, such as sheep or cattle, have a primary stomach (called the rumen) in which grass, which is almost the only food they eat, quietly ferments. The rumen is a sort of continuous culture of anaerobic microbes, including protozoa and bacteria, which collectively ferment the starch and cellulose of grass to yield fatty acids, methane and CO2.

In this chapter I shall consider the place of microbes in the evolutionary sequence of living things and attempt to assess what importance they had in influencing the directions which biological evolution has taken. Since I shall be dealing with questions that cannot usually be verified experimentally – for I shall be mainly concerned with events that took place in the darkest recesses of prehistory, even before recognizable fossils were formed – I must recall to readers the warning I gave about scientific fact early in this book. Even in everyday matters, laboratory science contains elements of uncertainty, particularly in interpretation of experimental findings. When one is concerned with retrospective deduction from today's knowledge about the state of our planet during its juvenile millennia, interpretation is so uncertain a process that it amounts to informed speculation. The surprising thing, really, is that one can say anything at all about the biology of those distant eras. Yet, as the reader will see, if one accepts geologists' views about the broad outlines of this planet's geological history, one can put together a coherent and reasonably plausible account of how the earliest living things developed. Whether it bears any relation to the truth is another matter, but it is a form of speculation that widens our understanding of life and its potentialities, as well as exercising the imagination. So, for this chapter, I shall relax scientific puritanism and see what sort of theoretical picture can be built up about the infancy of terrestrial life and the way in which today's microbes arose.

This is a book about germs, known to scientists as microbes (or to some, who cannot use a short word where a long one exists, as microorganisms). These creatures, which are largely invisible, inhabit every place on Earth where larger living creatures exist; they also inhabit many parts of the Earth where no other kinds of organism can survive for long. Wherever, in fact, terrestrial life exists there will be microbes. Conversely, the most extreme conditions that microbes can tolerate represent the limits within which life as we know it can exist.

The biosphere is the name biologists give to the sort of skin on the surface of this planet that is inhabitable by living organisms. Most land creatures occupy only the interface between the atmosphere and the land; birds extend their range for a couple of hundred metres into the atmosphere, burrowing invertebrates such as earthworms and nematodes may reach a few metres into the soil but rarely penetrate further unless it has been recently disturbed by man. Fish cover a wider range, from just beneath the surface of the sea to those depths of two or more kilometres inhabited by specialized, often luminous, creatures. Spores of fungi and bacteria are plentiful in the atmosphere to a height of about a kilometre, blown there by winds from the lower air. Balloon exploration of the stratosphere as long ago as 1936 indicated that moulds and bacteria could be found at greater heights; more recently the USA's National Aeronautics and Space Administration has detected them, in decreasing numbers, at heights up to thirty-two kilometres.

One statement can be made with as great certainty as any other in this book: short of some cosmic catastrophe, such as the sun becoming a nova, microbes on this planet have a future. This is more than can be said for many animals. It is highly probable, for example, that the days of the mountain gorilla and bonobo chimpanzee are numbered. Though attempts are regularly made to control hunting and poaching, it is unlikely that they will succeed while war and civil strife cause whole populations to hunger for ‘jungle meat’. Likewise the rhinoceros, the pangolin, the osprey and at least a hundred and fifty other large mammals and birds are destined to disappear from this planet unless they are successfully preserved in zoos or game reserves; only whales have attracted sufficient international attention for their anthropogenic decline to have been halted – if only briefly. Immensely greater numbers of lesser-known species of animals and plants are likely to vanish, unnoticed except by biologists, as mankind colonizes and modifies the more remote habitats of this planet; the environmentalist Paul R. Ehrlich has asserted that one in ten of the known plant species is threatened. But it was always so: throughout biological evolution, natural selection has involved an unceasing succession of extinctions and emergences of species; mankind has merely distorted the process, in recent centuries rather drastically. Is the startling variety of dogs, brassicas and the like, which our unnatural selection has generated, a sort of compensation, I wonder? Forgive the side-issue.

microbes and raw materials

Despite today's massive production, through the agency of microbes, of fermented foods and drinks, of antibiotics, vitamins and chemicals, it remains true that the most important microbial products, as far as mankind is concerned, were laid down millions of years ago.

Before I justify that assertion, I have a digression to make. Industry consumes energy, by using manpower, animal power, wind power or machinery driven by fuel such as petrol or electricity. The more sophisticated an industry becomes, the more it is likely to use mechanical power and therefore fuels. I am sure I need not offer the reader examples of this principle: choose almost any industry and reflect on its history. Indeed, it has become a commonplace of sociology to express the level of industrial development of a country or community in terms of the energy (excluding manpower and animal power) consumed per head of the population. Today, energy is needed for every facet of industrialized civilization, from boiling potatoes to pressing steel. This is why developing countries become obsessed with hydroelectric schemes, power stations and so on. Even food production, the basic process of society, becomes increasingly energy-consuming as it becomes more mechanized. Manpower, helped by domesticated animals, can support small agrarian communities, but as soon as the population increases and social organization becomes at all complex, communities come to depend on machines, fertilizers, chemicals and, therefore, on the energy that drives and produces these things.

The major energy sources of the world today fall into two classes.

I grew up in an area when science and technology, inseparable in most people's minds (including my own), were wonderful things. I suppose one has to be tapping on towards eighty to remember the time when an aeroplane was a thing to be stared at, when the crackling wireless was a miracle, when funny bug-eyed cars edged horses to the side of the road, when one or two of one's friends had tuberculosis, and telephones looked like black daffodils made of weird material called Bakelite, originating from coal-tar. As the 1920s segued into the 1930s the seeds of modern communication, travel, medicine and plastics were germinating and scientists were leading society to a new and glorious dawn; mankind would live well-nourished, well-cared-for lives in a happy technological Utopia, fulfilling its creative potential in arts and science, untroubled by war, deprivation, hunger and cruelty, for there would be enough of everything for everyone. Bigotry, prejudice and vindictiveness would vanish as scientific rationalism prevailed, putting flight to tribalism and mysticism (dignified by the uninformed as patriotism and religion). H. G. Wells was our prophet and, though we may not have followed his ideas in every way, none of us doubted that science, technology and the well-being of mankind went hand-in-hand, with man himself most in need of shaping up.

How innocent we were! For today there is a positive surge of feeling against science. Science, to many, has generated the threat of atomic holocaust, destroyed the environment, released new poisons, carcinogens and illnesses on an innocent and unsuspecting public and has done nothing to alleviate the perennial plagues of society: unemployment, poverty, drug abuse and violence.

In the early 1950s I was involved in the foundation of the National Collection of Industrial Bacteria (NCIB), a sort of bank established in Britain from which strains of industrially significant microbes could be obtained. Today it has grown into the National Collection of Industrial and Marine Bacteria (NCIMB) in Aberdeen and it is part of a valuable network of collections of microbes. The NCIMB has an important function: not only does it act as a reserve of organisms used in industry and non-medical research, but it also keeps typical bacteria involved in spoilage and deterioration, so that technologists can obtain reference strains to compare with those which may be causing trouble. In the early days of the NCIB's existence, parties of visitors used to come to see it. On one occasion a small party of civic dignitaries and their wives visiting the locality from France came round. I never clearly understood why, as it seemed a rather soggy sort of entertainment for the local municipality to arrange. However, I well recall the alarm shown by the wives when, not having at first understood the word bactéries, they suddenly realized they were amid a collection of germes. As one woman they pulled out handkerchiefs, covered their noses and left as soon as they politely could.

Laymen always associate bacteria, microbes and germs with disease. Microbes seem to have a faintly alarming or disgusting aura, and the fact that by far the majority are nugatory or even beneficial is rarely understood. Yet it is so.

Introduction

Asexual sporulation is generally the most prolific reproductive mode for fungi. Asexual spores of higher fungi are called conidia, which are non-motile asexual propagules made from the side or tip of specialized sporogenous cells and do not form through progressive cleavage of the cytoplasm. The process of conidiation is complex and involves temporal and spatial regulation of gene expression, cell specialization and intercellular communication. However, the genetic mechanisms controlling fungal sporulation have only been addressed in detail in two wellstudied ascomycetes, Aspergillus nidulans and Neurospora crassa. In this chapter we will describe the genetic regulation of development in A. nidulans. It is presumed that variations on this theme will apply in many cases to understanding conidiogenesis in other fungi as well.

The A. nidulans asexual reproductive cycle can be divided into three conceptual stages: (1) a growth phase that is required for cells to acquire competence to respond to induction signals; (2) initiation of the developmental pathway; (3) the events leading to sporulation.

Colony formation

Vegetative growth in A. nidulans begins with the germination of a spore. Spore germination leads to the formation of tubular structures, termed hyphae, that grow in a polar fashion by apical extension to form a network of interconnected hyphae known as a mycelium. The mycelium forms a radially symmetrical colony that expands indefinitely at a constant rate of about 0.5 mm h-1 (at 37 °C).

The fungi are admirably equipped with an array of degradative and lytic weaponry to colonize and enter the animal body. The host, of course, has an equally impressive armoury not only of defensive, but also aggressive machinery to prevent such an invasion. Very few fungi are obligate animal pathogens, but many are opportunists, able to take advantage of any chink in the host's defences.

Fungal infections of humans

The dermatophytes

The dermatophytes are a group of fungi which are particularly well adapted for the infection of the superficial keratinized structures of the body, including the nails, hair shafts and the stratum corneum (the cornified layer) of the skin. The true dermatophytes all belong to one of three genera of fungi, and are all able to use keratin as a source of nutrients. They are distinguished from a number of other fungi which may colonize the same superficial sites, including Candida albicans, Malassezia furfur and Aspergillus spp., by the fact that the dermatophytes are not opportunists. They are well adapted to their pathological niche and able to infect the immunocompetent individual.

The three genera of dermatophytes are Trichophyton, Epidermophyton and Microsporum, which together contain over 40 species. These organisms are relatively similar, but can be distinguished by colony morphology, macroscopic appearance and some biochemical tests. Recently, discovery of the perfect, or sexual, stage of several species of dermatophyte has led to their reclassification into two new genera, Arthroderma, containing the perfect Trichophyton species, and Nannizzia, containing the perfect Microsporon species.

Introduction

Fungal species have been at the forefront of developments in microbiology in particular and biology in general ever since the middle of the sixteenth century. Fungi have vital roles in agriculture, medicine and biotechnology. This chapter provides an overview of the role of microbiology in history with emphasis on eukaryotes. After a short introduction into what microbiology encompasses, a historical survey of some milestones in the development of modern microbiology, especially mycology, is given. This also describes where other scientific fields were influenced by fungal research.

Microorganisms and microbiology

Microorganisms are the most widely distributed group of living beings. They are capable of occupying nearly every ecological niche due to the fact that individual microorganisms can grow under extreme conditions, such as temperatures ranging from – 15 °C to more than 100 °C, or in the absence of oxygen or light. Neither animals nor plants are so adaptable; this is also true as regards nutrition. Some microorganisms can even utilize exotic energy sources such as alkanes, inorganic salts, or substituted aromatic compounds.

Generally, the term ‘microorganism’ encompasses all living beings too small to be seen by the human eye without magnification, i.e. smaller than about 1 mm. They are either prokaryotic, e.g. bacteria, or eukaryotic, e.g. hyphal fungi, yeasts and protozoa. We focus here on fungi and yeasts. For historical reasons the term ‘fungus’ is used for filamentously growing microorganisms, whereas yeasts are single-celled eukaryotes. However, taxonomically both are fungi (see Chapter 2).