Nature's Secret Gardeners--Fungi

"Formosa's envoys from dust to dust,/ Tiny beings, agents of renewal,/ Connecting the links of matter, propelling the circulation of energy,/ Decomposing life, returning it to the earth./ From slime molds to yeasts,/ From penicillium to silver ears,/ From veiled lady to field mushrooms,/ From parasites to saprophytes,/ From purple reishi to abalone mushrooms,/ From enchanting and poisonous toadstools of the wilds to delectable mushrooms of the kitchen."-Yi Ke-pao

Who else understands fungi as well as the Buddha and the poets? Surely the biologists.

Checks and balances

For the last 20 years, pine trees throughout East Asia have been withering and dying as if stricken by a plague, their many shades of green fading to lifeless brown.

The pine wood nematode (Bursaphelenchus xylophilus), a tiny worm less than 0.1 millimeters long, was carried from North America to Japan, from where it spread to Taiwan and on into mainland China. When infested by this alien nematode, centuries-old pines succumbed in droves. Agriculture and forestry agencies throughout East Asia joined forces to combat this enemy, but to little avail. They could only look on helplessly as the pine forests were ravaged by the worm's onslaught. But in the millennium year Professor Tseng Hsien-hsiung of National Taiwan University's Plant Pathology and Entomology Department and his research students discovered under the microscope a fungus which offers new hope for the pines' survival.

They discovered that a batch of nematodes were parasitized and killed by an unidentified fungus whose adhesive hyphae attached themselves to the worms. If this first known natural enemy of the pine wood nematode can be developed into a biological control agent, it may reduce the pines' death rate. Early this year, the Ministry of Economic Affairs' Food Industry Research and Development Institute (FIRDI) filed patent applications on this fungus in countries where the nematode occurs. Tseng Hsien-hsiung named the fungus Esteya vermicola after his Canadian teacher Professor Ralph H. Estey, in recognition of the latter's contribution to microbiological research.

There is still a long way to go before E. vermicola can be developed into a biocontrol for the pine wood nematode. But this fungus, which the electron microscope reveals to have a stalk like a mushroom and a cap shaped like a traditional Chinese gold or silver ingot, is just as much an endemic species, unique to Taiwan, as the treasured Formosan sika deer or Formosan landlocked salmon. Without it, the world would be poorer by one precious species, one set of genetic code.

Five kingdoms

For most of history, the limited powers of our unaided senses left humans blissfully unaware of the micro-organisms all around us. But the development of optical instruments gradually lifted the veil from that hidden world, so that human ideas about life had to be constantly revised. In taxonomic terms, life on Earth was no longer limited to the animal and plant kingdoms, but new kingdoms-fungi, bacteria, and protoctista (protozoa, algae etc.)-had to be recognized, to bring the total number to five. Each of the kingdoms of micro-organisms is just as gigantic, rich and complex as the plant and animal kingdoms.

Fungi are single- or multi-celled organisms with a distinct cellular nucleus enclosed in a nuclear membrane. In evolutionary terms they fall part way between the bacteria on the one hand and plants and animals on the other. Like bacteria and viruses, fungi cause many plant and animal diseases. They cause much damage to agricultural crops and are responsible for human afflictions such as athlete's foot and many other skin diseases.

But actually only a few of the fungi all around us are harmful to human health, while the number that studies show to be "friendly" seems to be growing exponentially.

Fungi are spread by spores, which may settle anywhere. The spores grow into microscopic filaments called hyphae, which may mass together and differentiate to form umbrella-shaped fruiting bodies, which in turn produce spores to continue the reproductive cycle. Tasty mushrooms are the fruiting bodies of fungi. Chinese veiled lady (Dictyophora indusiata), French truffles and Japanese pine mushrooms (Trichloma matsutake) all played important roles in early human gastronomic culture, and today remain internationally famous delicacies. The "half-insect, half-fungus" caterpillar fungus (Cordyceps sinensis), parasitizes caterpillars to produce its fruiting body.

Little money trees

Large fungi, such as shiitake mushrooms (Lentinus edodes) and reishi mushrooms (Ganoderma lucidum), in fact account for less than a fifth of the fungi. Most are invisible micro-organisms, such as the familiar molds, yeasts and "red yeast" (actually a mold, Monascus spp.).

Humans also long ago discovered-without understanding why-that these invisible little life-forms could do them good service. For instance, the Chinese used fermentation by fungi to make vinegar, monosodium glutamate and soya sauce, and red yeast to make food dye and honglujiu, a red rice wine. Pharmacopeias of traditional Chinese medicine include over a dozen fungi.

Modern genetic engineering is turning fungi into "money trees." In the 1970s, a retired Japanese professor was reading classic Chinese herbal pharmacopeias in search of medicines which could stimulate blood circulation. He found references to red yeast, from which he isolated compactin, a constituent with the ability to reduce blood cholesterol. Later the drug company Merck extracted the cholesterol-lowering drug lovastatin from a similar mold, Aspergillus terreus; the drug earns the company over US$200 million a year in sales revenues.

Penicillin, which was developed during World War II, is extracted from green penicillium molds, which grow on bread and fruit. Penicillin stops infectious bacteria from building their cell walls, and thus prevents them from reproducing. To date, penicillium mold has saved millions of lives. Antibiotics are deservedly called the drugs of the century. 80% of them are derived from fungi of the class Actinomycetes.

God's gift

How do tiny fungi produce such remarkable medicinal effects, making them the saviors of mankind? Tseng Hsien-hsiung, who is president of the Mycological Society of the ROC, explains that "secondary metabolites"-byproducts of metabolism-secreted by fungi are powerful weapons which fungi use to defend themselves against their enemies. They include antibiotics, toxins, radioactive substances and even hallucinogenic chemicals, which is why many mushrooms and toadstools are not safe to eat. Thanks to these metabolites, fungi are highly resilient organisms which can adapt to all sorts of adverse conditions. Some can survive in strongly acidic environments, in low-oxygen environments or at extremes of temperature. Today, with biotechnology developing rapidly, these "super-powers" are much coveted by researchers.

"Bacteria and viruses are structurally and genetically simple, with relatively small genomes. But when it came to fungi the creator used a lot of extra design tricks, and endowed them with many strange pieces of genetic information which other micro-organisms lack," says Tseng Hsien-hsiung. Tseng also indicates a further reason why scientists are fond of fungi: compared with bacteria and viruses, which are extremely difficult to observe, fungi are much easier to grow, manipulate and modify in the laboratory, and to produce in large quantities by fermentation.

As well as their contribution to medicine, fungi are being widely used to address the ills of modern society. In such areas as biocontrols, breaking down various pollutants and toxic pesticides and absorbing heavy metals, fungi have already made countless contributions to the "knowledge economy." "Why go to the trouble of synthesizing something if a bug can make it for you?" These words written by a geneticist in 1929 seem to predict today's international race to identify new fungi.

Inexhaustible riches

There are estimated to be least a million species of fungi on Earth, but to date less than 60,000 have been named. Among the countless natural habitats so far uninvestigated by humanity, there are many microbiological "black holes" waiting to be explored. As one biologist put it, microbiologists needn't worry about having nothing to do for the next 200 years.

But just as with other natural resources, the greatest microbiological riches are concentrated in developing countries, and these poor countries do not have the means to screen their own resources and develop useful biological agents. But the major pharmaceutical companies of Europe and North America have long been gathering rich pickings from these countries, by collecting large quantities of soil, humus and plant samples to use in the search for new drugs. This has brought them substantial profits, but in the past the countries owning the resources benefited little.

The UN Convention on Biological Diversity stresses the principle of shared benefits, and today many countries are beefing up the protection of their own microbiological resources, and introducing restrictions on the transfer of micro-organisms abroad. The first application of the convention to fungi was a deal signed between Merck and Costa Rica under which the pharmaceuticals company paid Costa Rica US$1 million for the right to collect soil samples there over two years, and also has to pay Costa Rica 5% of its profits on any product based on those samples which comes to market.

What do you know about Taiwan's fungi?

Taiwan's micro-organisms have also long been "plundered" by drugs companies. Twenty years ago the American pharmaceutical research company Panlabs set up a branch here to collect soil samples from all over the island and screen them for micro-organisms which might be used to produce drugs and biocontrols.

Three years ago, the Council of Agriculture commissioned researchers to make a survey of Taiwan's fungal resources. The survey recorded over 5,300 fungus species, of which a seventh are endemic to Taiwan and a quarter were new to science. Most Taiwanese mycologists have published descriptions of at least ten to 20 new fungus species. But extrapolating on the basis of a ratio of fungi to plants of six to one, "Taiwan should have at least 20,000 species of fungus," says Yan Gwo-fang, a senior scientist fellow at FIRDI's Culture Collection and Research Center (CCRC). In Yan's experience, German and Japanese biologists love to come "treasure hunting" in Taiwan, and when they have finished their collecting they are sure to tell her they have found "something new!"

In the past there was little awareness in Taiwan of a need to protect its fungi, but under pressure from the UN biodiversity convention, government agencies have recently proposed legislation to protect microbiological resources. However, legislating takes time. "The number of micro-organisms is vast. Patent rights for discoverers of new species are recognized internationally, so at present we take the approach of first filing patent applications for fungus species newly discovered in Taiwan which have potential for product development," says Yuan Gwo-fang, who rushed to apply for patents on Estey vermicola for Tseng Hsien-hsiung. She says that as well as pushing for reasonable legislation to protect Taiwan's interests, academics and research establishments are also working hard to collect and protect native fungi.

Culture collection center

At present there are 490 microbiological culture centers internationally which specialize in collecting and maintaining all kinds of micro-organisms. Fifteen years ago the CCRC was set up to collect and preserve fungi and bacteria. As well as isolating and authenticating microbial strains, the center also supplies microbes to research establishments and private industry. In the early days, most of the micro-organisms held by the center were types widely used internationally such as yeasts and red yeasts. But in recent years, in the interests of preserving biodiversity and protecting native resources, the center has reorganized and is directing the major part of its efforts towards developing native fungi. "Native and marine micro-organisms will be the main focus of our future work," declares the center's mission statement.

Yuan Gwo-fang says self-confidently that compared with other countries with rich microbiological resources, Taiwan has a reasonable level of scientific and technical development. Biotechnology researchers should pay attention to our native resources and develop new products from them. Otherwise if we merely snatch a little material from other countries to research, we are unlikely to produce useful results. Antrodia cinnamomea, a fungus which grows on the cassia tree species Cinnamomum kanehirae, is endemic to Taiwan, and is rumored to be effective in treating liver cancer. Apart from private-sector firms flocking to produce so-called health foods from A. cinnamomea, the CCRC is also making a major effort to research the fungus in the hope of developing a safe and effective scientific drug.

Enriching the soil

As the commercial potential of fungi is realized, biologists are also discovering the irreplaceable role that fungi play in ecologies.

Chang Tun-tschu is head of the Division of Forest Protection at the Taiwan Forestry Research Institute. When out in the countryside he loves to closely observe saprophytic fungi growing on dead wood. Chang explains that fungi can be broadly divided into parasitic (feeding on living organisms), saprophytic (feeding on dead organic material) and symbiotic types. The roots of 95% of all land plants live in a symbiotic-i.e. mutually beneficial-relationship with "mycorrhizal" fungi, whose hyphae surround or infiltrate the roots to form mycorrhizae ("fungal roots"), which enhance the plants' ability to absorb water and nutrients, and to resist drought. The natural antibiotics the fungi produce also help the plants to fight off pathogens. If the soil fungi are removed from plants' roots, the plants wither and die.

In the natural cycle of life, saprophytic fungi are also indispensable. If it were not for the work they do decomposing organic materials, the nutrients bound up in dead forest matter could not be released to enrich the soil, and the natural world would become cluttered with the debris of dead plants and animals. From birth to death, nature cannot do without these little citizens of the world.

But sadly, for lack of adequate research, many countries-Taiwan included-are unable to clearly map the distribution of their fungi, and still less to say how many unrecorded fungus species are being lost through the destruction of habitats.

Antrodia cinnamomea, the cassia tree fungus in which medical researchers are placing such high hopes, is one species facing the threat of extinction. A. cinnamomea grows only on Cinnamomum kanehirae, but C. kanehirae has the best timber quality of all Taiwan's broad-leaved trees, and to this day is still falling prey to illegal logging. The disappearance of its host has decimated the population of the fungus, while the fungus itself is also subject to excessive collection by the public. Both tree and fungus have become rare species. Chang Tun-tshu suggests that perhaps Taiwan, like European countries, should list its rare fungi in a Red Data Book, and give them legal protection.

Co-evolution

Human appreciation of fungi should not focus only on their utility and productivity. "If humans could see the microcosmos with their own eyes, on looking closely they would realize that this bustling universe made up of nothing but tiny micro-organisms, like a fine pointillist painting." (Retranslated from the Chinese.) In Microcosmos: Four Billion Years of Microbial Evolution, authors Lynn Margulis and Dorion Sagan say that plants and animals emerged from the "co-evolution" of fungi and algae. Without the pioneering efforts of micro-organisms, our distant ancestors could not have emerged from the sea to embark on the daunting task of conquering the land.

The great, blossoming garden of life emerged out of the teamwork of micro-organisms. The next time you pick up a handful of soil or raise a glass of water, perhaps, like the Buddha, you will see that the soil is not just soil, and the water not just water-they are teeming with life.

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The destruction wrought on pine forests by the pine wood nematode has brought an ecological crisis for East Asia. (facing page, photo by Vincent Chang) But plant pathology professor Tseng Hsien-hsiung may have discovered the nematode's nemesis: this micrograph shows the crown-shaped adhesive bud of a native Taiwanese fungus sticking fast to the nematode's body. (above, courtesy of Tseng Hsien-hsiung)

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Fungi are the Earth's model workers. Without them, 95% of plants could not survive, and the world would be cluttered up with the undecomposed debris of dead organisms; without them, humans could not produce many foods and condiments, and would have to go without many health-promoting and life-saving drugs. (photos this page courtesy of Chang Tun-tschu)

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As awareness of biodiversity issues has grown, culture collection centers have become involved in the preservation of species away from their native habitats. In Taiwan, the Food Industry Research and Development Institute's Culture Collection and Research Center preserves all kinds of microorganisms at low temperatures sealed in vacuum tubes.

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"Half insect, half fungus," the caterpillar fungus has long been used medicinally by the Chinese.

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Taiwan is blessed with both abundant natural resources and skilled research personnel, giving it the potential to develop localized research. Pictured here are staff at the Culture Collection and Research Center.