World Of The Fungi
It is worthwhile to examine more deeply this strange world, with such peculiar characteristics, and try to highlight those elements that somehow may be pertinent to the problems of oncology.
- Fungi are heterotrophic organisms and therefore need, as far as nitrogen and carbon are concerned, pre-formed compounds. Of these compounds, simple carbohydrates, for example monosaccarides (glucose, fructose, and mannose) are among the most utilised sugars. This means that fungi, during their life cycle, depend on other living beings, which must be exploited in different degrees for their feeding. This occurs both in a saprophytic way (that is, by feeding on organic waste) and in a parasitic way (that is, by attacking the tissue of the host directly).
- Fungi show a great variety of reproductive manifestations (sexual, asexual, gemmation; these manifestations can often be observed simultaneously in the same mycete), combined with a great morphostructural variety of organs. All of this is directed toward the end of spore formation, to which the continuity and propagation of the species is entrusted.
- In mycology, it is often possible to observe a particular phenomenon called heterocarion, characterised by the coexistence of normal and mutant nuclei in cells that have undergone a hyphal fusion.
Nowadays, phitopathologists are quite worried about the creation of individuals that are genetically quite different even from the parents. This difference has taken place by means of those reproductive cycles, which are called parasexual.
The indiscriminate use of phitopharmaceuticals has in fact often determined mutations of the nuclei of many parasite fungi with the consequent creation of heterocarion -- and this is sometimes particularly virulent in its pathogenicity. (4)
- In the parasitic dimension, fungi can develop from the hyphas more or less beak-shaped specialised structures that allow the penetration of the host.
- The production of spores can be so abundant as to always include, at every cycle, tens, hundreds, and even thousands of millions of elements that can be dispersed at a remarkable distance from the point of origin (a small movement is sufficient, for example, to implement immediate diffusion).
- Spores have an immense resistance to external aggression, for they are capable of staying dormant in adverse conditions for many years, while preserving unaltered their regenerative potentialities.
- The development coefficient of the hyphal apexes after the germination is extremely fast (100 microns per minute under ideal conditions) with ramification capacity, thus with the appearance of a new apex region that in some cases is in the neighbourhood of 40-60 seconds (6).
- The shape of the fungus is never defined, for it is imposed by the environment in which the fungus develops.
It is possible to observe, for example, the same mycelium in the simple isolated hyphas status in a liquid environment or in the form of aggregates that are increasingly solid and compact up to the formation of pseudoparenchymas and of filaments and mycelial strings (7).
- By the same token, it is possible to observe in different fungi the same shape whenever they must adapt to the same environment (this is called dimorphism).
The partial or total substitution of nourishing substances induces frequent mutations in fungi, and this is further proof of their high adaptability to any sub-strata.
- When the nutritional conditions are precarious, many fungi react with hyphal fusion (among nearby fungi) which allows them to explore the available material more easily, using more complete physiological processes.
This property, which substitutes co-operation for competition, makes them distinct from any other microorganism, and for this reason Buller calls them social organisms (8).
- When a cell gets old or becomes damaged (i.e. by a toxic substance or by a pharmaceutical) many fungi whose intercellular septums are provided with a pore react by implementing of a defence process calledprotoplasmic flux through which they transfer the nucleus and cytoplasm of the damaged cell into a healthy one, thus conserving unaltered all their biological potential.
- The phenomena regulating the development of hyphal ramification are unknown to date (9). They consist either of a rhythmic development, or in the appearance of sectors which, though they originate from the hyphal system, are self-regulating (10), that is, independent of the regulating action and behaviour of the rest of the colony.
- Fungi are capable of implementing an infinite number of modifications to their own metabolism in order to overcome the defence mechanism of the host. These modifications are implemented through plasmatic and biochemical actions as well as by a volumetric increase (hypertrophy) and numerical hyperplasy of the cells that have been attacked (11).
- Fungi are so aggressive as to attack not only plants, animal tissue, food supplies and other fungi, but even protozoa, amoebas and nematodes.
Fungi hunt nematodes, for example, with peculiar hyphal modifications that constitute real mycelial criss-cross, viscose, or ring traps that achieve the immobilisation of the worms, as a precursor their hyphal invasion.
In some cases, the aggressive power of fungi is so great as to allow it, with only a cellular ring made up of three units, to tighten in its grip, capture and kill its prey in a short time notwithstanding the prey's desperate struggling.
From the short notations above, therefore, it seems fair to dedicate a greater attention to the world of fungi, especially considering the fact that biologists and microbiologists constantly highlight large deficiencies and voids in all their descriptions and interpretations of the fungi's shape, physiology and reproduction.
So the fungus, which is the most powerful and the most organised micro-organism known, seems to be an extremely logical candidate as a cause of neoplastic proliferation. Imperfect Fungi (so called because of the lack of knowledge and understanding of their biological processes) deserve particular attention since their essential prerogative sits in their fermentative capacity.
The greatest disease of mankind may therefore hide within the small cluster of pathogenic fungi, and may be after all be located with just some simple deductions able to close the circle and providing the solution.
Considering that, among the human parasite species, the Dermatophytes and Sporotrichum demonstrate an excessively specific morbidity, and that experience shows that Actinomycetes, Toluropsis and Hystoplasma rarely enter the context of pathology, the Candid Albicans clearly emerges as the sole candidate for tumoral proliferation.
If we stop for a second and reflect on its characteristics, we can observe many analogies with neoplastic disease. The most evident are:
- Ubiquitous attachment: no organ or tissue is spared
- The constant absence of hyperpyrexia
- Sporadic and indirect involvement of the differential tissues
- Invasiveness that is almost exclusively of the focal type
- Progressive debilitation
- Refractivity to any type of treatment
- Proliferation facilitated by multiplicity of indifferent cofounders
- Symptomatological basic configuration with structure tending to the chronic
Therefore an exceptionally high and diversified pathogenic potentiality exists in this mycete of just a few microns in size, which, even though it cannot be traced with the present experimental instruments, cannot be neglected from the clinical point of view.
Certainly, its present nosological classification cannot be satisfactory, because if we do not keep the possibly endless parasitic configurations in mind, that classification is too simplistic and constraining.
4) Rambelli A., "Fondamenti di micologia", Bologna 1981, page 35
6) Ibid., page 28
7) Verona O., cit. page 5
8) Rambelli A., cit. page 31
9) Ibid., page 28
10) Ibid., page 29