LIVING WITH IT WORKING WITH IT TREATING IT
Discovery of cyclosporine in 1971 began a new era in immunopharmacology. It was the first immunosuppressive drug that allowed selective immunoregulation of T cells without excessive toxicity. Cyclosporine was isolated from the fungus Tolypocladium inflatum. Cyclosporine was first investigated as an anti-fungal antibiotic but its spectrum was too narrow to be of any clinical use. J. F. Borel discovered its immunosuppressive activity in 1976. This led to further investigations into its properties involving further immunological tests and investigations into its structure and synthesis. Cyclosporine has unwanted side effects, notably nephrotoxicity. Animal testing showed cyclosporin to be sufficiently non-toxic to begin clinical trials. These initially failed due to poor absorption of the drug. Once this had been overcome, results were encouraging enough for cyclosporine to be licensed for use in clinical practice. There is some controversy between Borel and other workers over priority in the discovery of cyclosporine and its pre-clinical development, which is examined in this review. Cyclosporine changed the face of transplantation. It decreased morbidity and enabled the routine transplantation of organs that until then had only been done experimentally.
The medicinal value of shiitake is not really well appreciated in Western medicine, though it has a long history as a valuable remedy in traditional Asian medicine. Research on the chemicals present in Lentinula edodes seems to be revealing medical products and it may become a valuable resource in fighting diseases.
Fungi for better health and environment [downloads a PDF presentation showing an overview of fungi, their place in the natural world and impact on human affairs.]
The discovery of Diflucan (fluconazole) was a major landmark in the pharmaceutical industry, as it was the first antifungal drug to be developed that could be used both orally, for minor infections such as candidiasis, or intravenously for more serious systemic infection like cryptococccal meningitis.
Fluconazole development was based on two initial assumptions by the scientists involved: firstly that drugs should be tested in experimental models of infections, and secondly that a polar molecule might have superior pharmacological properties. The developers took these two ideas as a starting point and went through a rigorous process to find the right compound. Eventually they came across 2-(2,4-difluorophenyl)-1,3-bis (1H-1,2,4-triazol-1-yl)-2-propanol, that is fluconazole. This report details the progressive discovery of fluconazole and all the intermediate steps and compounds found along the way. The report also describes the general development of drugs, the history of antifungal agents of the past and examines the major agents currently available. There is also a section devoted to the clinical and pharmacological profile of fluconazole, and any considerations concerning the future development of antifungal agents.
Traditional Chinese medicine (TCM) uses many products derived from fungi, including Lentinula edodes (shiitake). Evidence, in the form of published papers, regarding its usefulness has been examined. The review finds that the anti-tumour claims are substantiated, especially those of the lentinan polysaccharide isolated from shiitake. Lentinan is also found to be an immunomodulator, although the medicinal value of these findings are yet to be reliably established. Cholesteremic effects were shown but there was disagreement over the details of the effects. It was concluded that Lentinula edodes does have much potential in medicine but further research is needed.
Ask about fungi and people think about fine specimens like these guys:
Ask to what they are related and you'll probably find that some people think fungi are plants...others think they might be bacteria.
‘How many of you think that fungi are bacteria?’ is a question posed at a recent Summer School for year 10 pupils (4th year in secondary school, and about 16 years of age at the time), by one of the pupils who had attended a workshop session of ours. When all attendees (approximately 170 pupils) were asked 'Hands up all those who think fungi are plants', about 15 hands went up, but when asked 'Hands up all those who think fungi are bacteria', at least 150 hands went up!
As teachers we are used to battling against the mistaken idea that fungi are plants, but it was a shock to find that so many pupils believe that fungi are bacteria so close to the end of their statutory education. After all, it’s a bigger error than for them to think that whales are fish; at least whales and fish are in the same biological Kingdom. Does such ignorance matter? We say it does. The practical reason it matters is because the activities of fungi are crucially important in our every day lives. The educational reason it matters is that fungi form what is arguably the largest kingdom of higher organisms on the planet. Ignorance of this kingdom is a major blot on our personal education.
Fungi are not bacteria, because fungi are eukaryotes and they have the complex cell structures and abilities to make tissues and organs that we expect of higher organisms.
Ergot is a fungal infection that has infected rye and other plants since farming began. One of the constituents of ergot, the ergot alkaloids, were found to have useful medicinal properties. Ergot was known to cause gangrene in the limbs of those who had ingested infected bread. But later its first medicinal property as a powerful oxytocic (facilitating childbirth) was discovered, and more recently its derivatives have been used in the treatments of migraine. It was the alkaloids of ergot that were found to be the active components in their pharmacological actions, starting with the first pure alkaloid to be isolated, ergotamine. This review covers the history of ergot and the ergot alkaloids and tries to show how ergot went from being just an infection of grass to its alkaloids being the active component in many drugs, especially those in the treatment of migraine. The mechanism of action of the ergot alkaloids is also explained.
Fungi have been influencing human affairs for thousands of years, whether as a direct food source, as a medicine, or in a food process . Today food of fungal origin is consumed all over the world in vast quantities, and commercial production is part of a rapidly growing industry. Fungi are of excellent value nutritionally, and of great importance to vegetarians. Edible mushrooms have high protein content, and are an excellent source of fibre, vitamins, and some minerals. Efforts to combat anticipated world food shortages, led to the production of ‘single cell protein’, grown in industrial fermenters using yeast cells. The result is a protein extract with high amino acid content potentially favourable for use in human nutrition. One particularly successful model was that of myco-protein, marketed as Quorn™. Essentially the mycelium of Fusarium venenatum, its filamentous nature much resembles the fibres of meat. Quorn is now available in supermarkets, marketed as a high-protein, low-fat, cholesterol-free ‘meat alternative’. When it comes to fungi as a food source, many people are apprehensive and much education is needed before the true nutritional value of such a cheap, readily available food source can be fully realised.
Our use of fungi is usually hidden from view, so the way we most often directly encounter useful fungi is as part of a meal of mushrooms!
All photographs © David Moore 2011
Mushroom cultivation is important, and I will say more about it below, but it's not the only way we can and do make use of fungi.
The story of the statin based drugs provides an interesting insight into the discovery and development of modern pharmaceuticals. As well as looking at the complexity of the technology and science involved, this Special Studies Module also looks at the time and resources that must be devoted to developing a marketable drug from an initial concept. Whilst the pharmacology of a specific family of drugs might be similar, small differences in molecular composition, and human physiology can substantially alter the overall effectiveness of the drug, and even classes of patient in which the drug might be of use.
Given the cost of development, many drugs will become unaffordable to a large proportion of the world population, even if the cost seems reasonable in terms of suffering and the palliative care that might have to be offered in their place. The problem of cost may also be exasperated as the development and marketing of new drugs often seems to be in the control of a handful of large multinational companies.
In November 2000 a report was commissioned by Cancer Research UK  to look at the potential of medicinal mushrooms in the treatment of cancer.
The aim of this Special Study Module (SSM) is to review and produce a report accessible to all members of the public, using that original report as the starting point. In addition it will look at the history of Chinese fungal remedies which dates far back into ancient times, and has formed the basis of the research in the report. The SSM will also look into the potential of use of fungal products in the NHS as well as their advantages and disadvantages.
The major findings of the report showed that there are certain compounds found in mushrooms that have an anti-cancer effect. These compounds are known as polysaccharides. They appear to act on the host’s immune system rather than directly on the tumour. The main polysaccharides that the report focuses on are Lentinan, Schizophyllan, PSK and PSP.
These polysaccharides have undergone several clinical trials and are showing good prospects for use in Western medicine. It is just a matter of whether the Western population will accept this method of treatment.
Fungi help the balance of nature by nutrient recycling. Fungi decompose things. Importantly, fungi are about the only organisms that can digest wood, because the lignin which is complexed with the cellulose in wood is so difficult to degrade. Lignin digestion is a fungal speciality but they gain nutrition from living or dead animals as well as plants, and the breakdown of other complex molecules such as cellulose and tannins in soils is due mostly to fungal enzymatic activity.
Fungi are all around us, and there are enormous numbers and quantities of them. It's been estimated that fungi make up 90% of the total living BIOMASS in forest soils. For grassland soils, another estimate puts the total length of hyphae at over 1 kilometre per gram weight!
There is such a large amount of fungal mycelium in most soils that it makes a major contribution to FOOD WEBS by being eaten by numerous vertebrates and invertebrates including insects, mites, molluscs and nematodes. Microarthropods are responsible for shredding organic matter in soil (and so prepare it for the final mineralization processes carried out by microbes), but about 80% of the tens of thousands of microarthropod species in forest soils are fungivores - they depend on the fungal mycelium for food.
When the mycelium makes fruit bodies (like mushrooms, brackets and truffles), these are also vital food sources for many animals, from mammals (including humans) to molluscs, as the following sequence of a slugfest shows ...
Statins only became really important as a treatment for hyperlipidaemia within the last decade of the twentieth century. They are fast progressing as one of the most interesting and useful family of drugs available and are likely to become the 'wonder drugs' of the twenty-first century. There have been a number of clinically important trials performed on statins within the last ten years each allowing a greater understanding of CHD, its causes and risk factors. Not only can they be used to effective treat those at high risk of CHD, they have also been investigated in conjunction with the treatment of osteoporosis, multiple sclerosis, Alzheimer’s disease and in reducing the unwanted increased incidence in CHD in women on HRT treatment. Not everything is such a rosy picture however, as recently one of the major statins has been removed from the market followed reports of muscle wasting and deaths.
This mycoses page is intended to give students (or anyone who's interested really!) some insight into the clinical aspects of mycology. This page covers an area of mycology which is more immediately interesting to most people.
Here you'll find details of diseases, the organisms that cause them, symptoms, and treatments. Hope you find the journey useful.
Kinetic analyses show that fungal filamentous growth can be interpreted on the basis of a regular cell cycle, and therefore encourage the view that mycelial growth and morphology can be described mathematically. Here, we review published mathematical models that attempt to describe fungal growth and branching in the vegetative (mycelial) phase.
Statins are a group of cholesterol lowering drugs that account for around 40% of prescribed drugs by GPs in the UK. The statin manufacturing industry is worth billions of dollars and is a growing industry. The link between increased LDL-cholesterol levels and the chances of developing coronary heart disease (CHD) has long been acknowledged. Given the high cost of CHD to the NHS (in 1985-86 it is estimated to have cost £390 million ), ways of reducing the burden are likely to become more and more necessary. In the UK, coronary heart disease (CHD) is responsible for 28% of all deaths, and 33% of deaths in men under 65 years old, making it the leading cause of death. Globally, CHD is also set to become a much larger threat. Whilst in 1990 pneumonia, diarrhoeal disease and perinatal conditions were the leading causes of death, it is predicted that by 2020 heart disease, depression and road traffic accidents will be the three greatest killers world wide.
In informal terms there are three major groups of fungi:
Whilst they all have different properties, they generally all share the key feature of the fungal lifestyle, which is the ability to decay organic matter as a means of accessing the nutrients that waste materials contain (saprotrophism).
In fact the recycling ability of fungi is the area that holds the prime interest for scientists today. Lignin is one of three components of plant cell walls (the others being cellulose and hemicellulose), and is a complex polymer which provides the strength and support in the secondary growth of perennial plants like bushes and trees; it is part of the woody tissue that makes timber as we know it. However, lignin is a complex polyphenolic; whilst it is of great use to all plants, it is a major problem for most microorganisms that try to access the nutrients inside the plant, but are foiled by the phenolic antiseptics released by any attempt to degrade its lignocellulose protective barrier. In fact, there is only one type of microorganism that can degrade lignin…and , yes, you guessed it…it's the fungi.
Microbiology online has been devised by the Microbiology Society, the largest learned microbiological society in Europe. This inspirational online resource supports the teaching and learning of microbiology in the classroom across the key stages. It explores how microbes can be friend and foe and most importantly, why we need these invisible organisms to live.
Resources for teaching mycology for UK key stages 2, 3 & 4 and post 16.
Website provided by the British Mycological Society
Roger Phillips' twenty-year study makes this site the most complete collection of photographs and mushroom information from both sides of the Atlantic ever assembled. We already have over 3000 images on our site to help you identify and learn more about the mushrooms of Europe and North America! RogersMushrooms is now completely free to access!
Website of the Fungal Cell Biology Group at the University of Edinburgh. The main focus of research is on developmental pathways resulting from conidial germination and the early stages of colony establishment in the fungal model Neurospora crassa and the human pathogen Aspergillus fumigatus. Much of the research involves analysing living cells using a wide range of advanced imaging and measurement techniques and the site is superbly illustrated with video and photographic results of these analyses.
You should be able to find everything you wanted to know about fungi by clicking on the on the links on the images or on the text links. Tom promises to leave his pages at this site for a long time, and points out that you can always find them by typing (no spaces) into your browser.
Photographs to delight. Taylor F. Lockwood states that the essence of his work is the appreciation of the beauty and variety of mushrooms and other fungi. His stunning photographs certainly manage that. With a background in music, art and the sciences he has become a naturally inspired promoter of a kingdom of species which deserves more attention than it has usually received in the past.
Nearly 5000 very fine photographs; well worth the visit.