Ancient Viagras --Biotech Breathes New Life into Chinese Herbal Aphrodisiacs

At the same time that the anti-impo-tency drug Viagra has been making its global splash in the world of medicine, here in the ROC both Taiwan Sugar Corp. and Union Chemical Laboratories at the Industrial Technology Research Institute have been working to mass-produce the treasured Cordyceps sinensis, a fungus used in Chinese herbal medicine to fortify the kidneys and revive flagging male libidos. Meanwhile, the National Research Institute of Chinese Medicine has been analyzing the pharmaceutical properties of herbal remedies claimed by ancient Chinese medical books to bolster virility. Several of their extracts have successfully risen to their first challenge-that of swelling the spongy tissue of the male rabbit's sexual organ.

There are countless Chinese folk virility potions and impotency remedies noted in classic Chinese medical texts. If the public wants proof of their miraculous claims, they'll just have to try them and see for themselves.

In the wake of the Viagra tidal wave, will the traditional Chinese herbal aphrodisiacs and impotency remedies that have been developed over millennia provide a new direction for biotechnology in Taiwan? And does the "golden spear" really provide an ideal focus for Chinese medicine?

When Viagra hit the market, it captivated the world as if it were some sort of magic bullet. Although there have been reports of people dying after taking it, the small pill is very convenient and swiftly effective. This superenhancer of sexual potency has emboldened and elated men, and the fanfare over its development shows no signs of abating.

Viagra has not been formally released in Taiwan, but pills go for NT$2000 each on the thriving black market. Police have already busted doctors for illegally selling the drug. Recently debate has raged over whether National Health Insurance ought to cover it.

Individual components have then been selected for testing on rabbit penis tissue （left）

Watch cable television and you're sure to see advertisements for "health foods" with names such as "Victorious Easterner," "Return of Spring," "Pill of the Green Dragons and Tigers" or "Thrust Eternal." All reputedly fortify the kidneys, cure sexual impotency and strengthen yang. (Yang is the masculine or bright part of the yin and yang. In traditional Chinese medicine a proper balance of yin and yang is considered important for good health. Impotency is often attributed to a lack of yang in related organs.) Taipei's Tihua Street is lined with the shops of traditional Chinese pharmacists. Here you can find deer penis, seal penis, horned toads, deer antlers and jar after jar of "three penis wine" with its dozens of different medicinal components. All are ancient Chinese impotency remedies that have been passed down for more than a thousand years.A golden spear that never droops?

Both in China and elsewhere the earliest aphrodisiacs and impotency remedies were all made from natural ingredients. In ancient Rome, edicts were often issued forbidding women to use aphrodisiacs because of their overly powerful effect. The sex drugs described in ancient Chinese texts seem a mixture of medicine, myth and superstition. One such wonder drug was claimed "to make one's pole stand out so straight that its shadow becomes visible" and to allow one "to fight 100 battles in nine nights with no loss of verve and leave the ladies with cherished memories of ten times a night. . . ."

The ancient Chinese erotic novel

Zhaoyang Qushi describes how the Han Emperor Chengdi's libido began to flag after excessive lovemaking with the sisters Zhao Feiyan and Zhao Hede. Shenyugao, an alchemist's concoction, revived him, turning him into a never-slacking warrior of a hundred nighttime battles. His downfall came when the nymphomaniac Hede secretly ground up seven portions of the miracle drug in the emperor's food and drink. He spurted semen like a spring spurts water-until he died. Among other traditional favorites are Jinqiang Budaowan (never-sagging gold spear pill), which is supposed to delay ejaculation; Yiduosan, touted to augment virility and restore youth; and Changyinfang (sexual-organ lengthener), claimed to increase penis size. There are also prescriptions for women, such as Yue, which is placed within the vagina to treat frigidity, and Zhaiyinfang (sexual organ narrower), which reputedly makes the vagina tighter. The claims made about each and every one of these medicines are so bold that they sound nothing short of the miraculous.

Yang Shih-fu, the third-generation owner of an herbal pharmacy on Tihua Street, remarks, "Many customers come in to buy medicine with prescriptions that include acrid or even toxic ingredients such as croton seeds, secretio bufonis and Xanthoxylum bungei. These are simply anesthetics that are applied to the reproductive organs. Herbal pharmacists don't recommend customers to take prescriptions of this ilk."

（right and below） In recent years the National Research Institute of Chinese Medicine has been researching traditional herbal virility prescriptions, carrying out compositional analysis on them.

Chen Chieh-pu, head of the National Research Institute of Chinese Medicine (ICM), notes that there are good points and bad points to traditional Chinese aphrodisiacs and remedies aimed at combating impotency or frigidity. Prescriptions like those described above that bring about long-term erections at the price of a loss of sensation seem far removed from the realm of beautiful feelings typically conjured up by the idea of sex. And the story of Emperor Chengdi's sexual hedonism seems to offer this moral: If virility prescriptions are used inappropriately, miracle drugs may end up turning into deathly poisons.Opening our ancestors' medicine jars

In treating a disease Western medicine usually focuses on the symptoms rather than the root cause. Viagra has created a worldwide sensation and delighted both men and women because it allows formerly impotent males to gain erections. Traditional Chinese herbal medicines, on the other hand, try to cultivate the channels of male potency within the body itself. Regarding sexual matters, Chinese medicine focuses on the shen or kidneys, which here are given a broader meaning that includes all of the organs connected to the urogenital tract as well as the adrenal glands. Consequently, in modern times few bona fide doctors of traditional Chinese medicine have been carrying out research on the specific-and what they regard as merely symptomatic-problem of impaired sexual function. Yet this absence of research has given rise to all manner of bizarre folk prescriptions and quack nostrums aimed at combating impotency. Users are left to determine for themselves whether any of these remedies actually works or if they have noxious side effects.

Three years ago, however, ICM began looking at ancient Chinese virility prescriptions. To achieve greater understanding about the efficacy of these traditional remedies, ICM researchers first extracted and analyzed their chemical components before testing them on animals. Chen Chieh-pu points out that these prescriptions developed from thousands of years of clinical experience and that the bioactive components in natural medicines have provided the basis for many newly developed drugs. But there is little in the way of scientific evidence and analysis about Chinese herbal medicines, and scant research into how their active ingredients achieve their effects.

ICM researcher Chen Ta-chih first studied both folk prescriptions and those prescriptions found in ancient medical texts. He discovered that just as modern Western treatments call for injections into the penis or doses to be taken directly in the urinary canal, ancient Chinese medical texts included many similar external applications to treat impotency. Chen looked at numerous herbal prescriptions to be taken before sex, which were designed to give men the ability to gain erections. He then selected those ingredients mentioned with high frequency and began research on them.

Every one of these herbs contains at least a thousand individual chemical components. Chen first grinds the herbs into powder and boils them in different solvents to obtain dry and concentrated initial extracts. Then Chiu Wen-hui carries out animal testing, individually applying these extracts to separate groups of rabbit penis tissue in vitro, so as to test their active effects. At this point the researchers make records and write reports that include graphs of the average swelling in each group and discussions about which chemicals are most active. The next step is to perform detailed chromatographic analysis, employing series of upwards of ten chromatographs to gradually screen out components until they are left with individual active chemical ingredients.

After identifying these, the researchers peruse the academic quarterlies to see if anyone has already extracted these components from herbal medicines. At this stage it is also essential to make certain that the substances aren't toxic and to determine if, apart from their effects on the penis, they affect any other organ.

It's all part of an effort to remove the veil of mystery obscuring Chine se Viagras.

Then pastes or medicated compresses containing the individual active substances can then be made for external application. ICM has already found two Chinese herbal medicines containing substances proven in experiments to have impressive effects on rabbit penis tissue. These have stirred hopes for a Chinese Viagra and caused people to describe this direction of research as one of the most promising for biotechnology in Taiwan.Biotech pot of gold?

Following the announcement that British researchers working for PPL Therapeutics had cloned a sheep and the marketing of Viagra by the Swedish firm Pfizer, the stock price of Entremed, a previously unknown pharmaceutical firm, recently tripled in one day after it announced that it had developed a new anti-cancer drug. Thought to have high growth potential, biotechnology stocks have become star performers. Firms developing protein drugs, genetically engineered vaccines and hormone drugs are growing particularly fast. Simply put, these firms use biotechnology to help people live longer and in better health.

As early as 1990, the Council for Economic Planning and Development in Taiwan designated biotechnology as one of the targets of its efforts to promote industrial development. In June of this year, at the Second Strategy Review Board for Biotechnology put on by the Science and Technology Advisory Group of the Executive Yuan, many foreign experts predicted that biotechnologically produced herbal drugs would enter the medical mainstream in the 21st century and that Taiwan should be quite competitive on this new industrial battlefield.

In biotech research involving Chinese herbal medicines, there are two basic directions: The first is to go the Western route by extracting components of herbal medicines, determining their molecular structures and active ingredients, and going on to develop drugs. Both in Taiwan and abroad there has been a lot of research of this kind into the fungus Ganoderma lucidum and the yew tree. Notably, a substance found in the bark of the yew tree has yielded the drug taxol, which is used to fight breast cancer.

Cordyceps sinensis, which originally grew in just a few spots on the Tibetan Plateau, is now being cultivated artificially with the help of biotechnology. This has resulted in a safe and reliable supply and also lower prices.

Yet, by going this way, taking Western techniques and methodology to screen Chinese herbal medicines, you've got to first know which diseases lead to which pathological mechanisms, and then, based on this mechanism, design a model for automatic screening and employ screening instruments so as to be able to extract a specific components from a multitude of natural ingredients. "Taking this route, we'll find it hard to keep up with the research of Western nations," argues Chang Chun-ming, a researcher of biotech applications at Union Chemical Laboratories. "Secondly, in trying to find specific components, we may end up casting aside combinations of ingredients that are valued in Chinese medicine, and thus lose other possibilities for research." Strength in numbers

Doctors of traditional Chinese medicine have always been great believers in pharmaceutical synergism, stressing the importance of adjuvants (substances that enhance the effectiveness of chiefly active ingredients) in designing optimal prescriptions.

"What makes Chinese medicine Chinese medicine? It is precisely this use of synergistic combinations of natural substances-both from animals and plants-as opposed to the use of individually active chemical substances," says Chang, who holds a doctorate in chemistry and is certified as a doctor of Chinese medicine. If only individual active components from herbal medicines are extracted and used, then the special synergistic character of herbal medicines will be lost.

Before researching Chinese herbal medicine, safe and stable supplies of herbs must first be established. Most of the plants used by Taiwan's herbalists come from mainland China. This makes both the supply and the quality unstable because the same plant grown in different regions, or under different weather and climatic conditions, will produce different medicinal effects. This makes necessary the use of biotechnology in the artificial cultivatation of Chinese herbal medicines.

Chinese medicine needn't go the way of Western medicine, using only transparently active individual chemical components. If chemical analysis is performed on a good quality herbal specimen, creating "a fingerprint" of its chemical components, this can then be used as a standard by which the artificially produced herb can be judged. Artificial cultivation will give researchers access to herbal medicines without the problems caused by regional and climactic variation, allowing them to proceed with animal testing and analysis of its medicinal effects. Even if complete understanding of exactly how a Chinese herbal medicine is working hasn't been obtained, this doesn't diminish the fact that it is working.

Chinese medicine uses Cordyceps sinensis to fortify the kidneys and treat asthma. Unfortunately, it grows naturally only in a few remote areas, and yearly harvests are small. Unscrupulous dealers use all manner of tricks to doctor the rare herb and raise their profits.

This process outlined above has been adopted for the fungus C. sinensis, which is used to fortify the lungs and kidneys and to treat impotency and asthma. Unfortunately, people are often poisoned by the lead that unscrupulous dealers add to increase the weight of this precious fungus. As a result, both Taiwan Sugar and Union Chemical Labs have researched how to use biotechnology to grow it artificially. Recently they have started mass production. Native of the Tibetan Plateau

Cordyceps sinensis-or dongchong xiacao (winter bug, summer grass), as it is known in Chinese-is a fungus described rather mysteriously in the Supplement to the Compendium of Materia Medica as "In winter a bug, in summer a grass, it has hair and can move." In actual fact, dongchong xiacao broadly refers to more than 300 different fungi that grow on insects, but the type used in Chinese medicine is a true fungus that grows on the larvae of bat moths. In the summer the fungus's spores scatter on the ground, attaching themselves to moths' larvae, which escape the ravages of winter underground. At this point, during the "winter bug" stage, C. sinensis begins to grow rapidly within the larva. Then in May or June of the following year, with the last of the snow still melting in the early summer, the sporocarp of the fungus shoots up above the ground. This is the "summer grass" stage, when people come to gather the fungus on their hands and knees in the snow, searching through the various grasses for this centimeter-long fungus. When they find it, they dig up both the fungus above the surface and the larva below.

According to the Supplement to the Compendium of Materia Medica and New Compendium of the Materia Medica, the fungus is mainly used to fortify the lungs and the kidneys and to treat a lack of yin in the lungs (as manifested in hacking coughs and expectoration of blood), and can also be used to treat impotence and premature ejaculation. Folk remedies frequently use it to treat asthma and sore backs.

Because it grows only in Qinghai, Tibet, Sichuan and Yunnan at an elevation of 3000-5000 meters, it has always been rather expensive. In 1993, when runners trained by mainland track coach Ma Junren broke world record after world record and Ma attributed their success to their taking C. sinensis, this rare and expensive fungus became highly sought after.

Traditional Chinese medicine doesn't look highly on prescriptions that t ry to help men get erections, for these are regarded as curing only the symptom of impotency. Chinese medicine aims instead to cure the root cause of illness by cultivating curative channels within the body. （photo by Vincent Chang）

Currently, a Taiwanese pound (600 grams) of the fungus fetches about NT$20,000. Some dealers have been known to weigh down larvae with lead or to mix in other similar larval fungae and starch. People end up getting both less C. sinensis than they have paid for and lead poisoning. And the few spots where you can find the fungus in the summer on the mainland are getting so picked over that "that there virtually isn't clump of grass that hasn't been upturned," says Yang Shih-fu, a Chinese herbal pharmacist who worries that declining harvests will imperil supplies.Test-tube fungus

Because this treasured ingredient of Chinese herbal medicines is of such uneven quality and so expensive, over the last three or four years Taiwan Sugar in southern Taiwan and Tah Chwen Food (an affiliate of Tah An Kong Yen Food) in northern Taiwan have each been working to produce the fungus artificially and thus overcome limitations caused by geography and harvest quantity.

The first step was to go to the mainland and obtain some natural dongchong xiacao, from which the living fungus was extracted. They then worked to get the fungus to grow continuously in the test-tube before moving on to fast mass production in industrial vats. When the sporocarps of the fungus are removed from the vats, it is necessary to separate them from the culture medium they feed on. When they have 100% fungus, the manufacturers turn it into dry powder and put it into capsules.

While the process may sound quite similar to typical fermentation techniques, it involves extracting high quality C. sinensis, the selection of appropriate different media for absorption by the fungae at different times and also the question of how to maintain a high level of oxygen in the tank without harming the fungus. Getting these right required a long process of trial and error. Otherwise, it wouldn't have taken three or four years to get to where they are now.

Entering a biotech factory producing C. sinensis, we are greeted with a scent redolent of grass and wood coming from large metal vats used to grow the fungus in mass quantities. In the vats, culture media serve as stand-ins for moth larvae. For every ton in the ITRI vats as many as 20,000 C. sinensis sporocarps can be produced in a day. And Taiwan Sugar already has orders for more than two tons of the fungal powder, which comes to roughly NT$10 million. "It's not necessary to go to the Tibetan Plateau and import the fungus. Today, it's available in Taiwan at a low price, and it is grown here under conditions that simulate those found in nature," notes Chang Chun-ming. "Being able to buy the C. sinensis with its quality assured is a benefit of biotechnology."

"One box of the fungus is 25 grams. The price of two boxes of the powder is equivalent to about a kilo of sugar," remarks Yang Po-wen, director of product processes development systems for Taiwan Sugar, by way of comparison. You can see that the production of the fungus has already become a goose that lays golden eggs. Using biotechnology to develop new products has become an important strategy for Taiwan Sugar, and the company has hired six new PhDs for this purpose.Grass or bugs?

But is the biotech fungus the same as nature's? Originally, the dongchong xiacao in Chinese medicine included both the "summer grass" of the sporocarp and also the "winter bug" of the moth larva, whereas now only the former is being synthesized in the laboratory. In which case, is it really the same as the dongchong xiacao used in herbal medicines? And is eating fungus that is artificially grown in culture media the same as eating fungus developed in a bat moth's larva? Some doctors of Chinese medicine and herbal drug experts have their doubts.

"The artificially produced C. sinensis not only has the same components as the dongchong xiacao found in nature, but in fact its purity and effects are better than nature's version." Two research organizations have come to the same conclusion on this point. Taiwan Sugar's Yang Po-wen explains that they used chromatographic analysis to compare the artificially produced fungus with its natural brother, and determined that its polysaccharides, minerals, vitamins and amino acids were virtually identical, and thus the two would bring the same effects.

Chang Chun-ming explains, "The C. sinensis we buy in herbal pharmacies is mostly the fungal growth of the 'summer grass.'" In fact, the nutritients from the larva of the "winter bug" have already been absorbed and transformed by the "summer grass." All that's left of the bug is the woody shell, which offers no more nutrition than dirt. While it may appear as if the shell is very nutritious, it's not the case. Even many herbal pharmacists are ignorant about this. "Once I went to a Chinese herbal pharmacy and I asked the proprietor if there were any loose bits of 'summer grass' for sale. He happily sold me a pile of broken bits of the 'grass' for next to nothing. He clearly didn't know if the good part was the larva or the fungus." Chan Chun-ming explains that with artificially cultivated C. sinensis you get the essence without the dregs. The purity is 100%, which is better than with nature's version. Good medicine, bad medicine

Although the ancient medical texts do describe C. senensis as good for the kidneys and a remedy for impotence, once the news media started billing the biotech version as the Chinese Viagra both Chang Chun-ming and Yang Po-wen came forward to declare that the fungus lacked Viagra's ability to quickly and directly bring about erections. Chen Chien-chih, who tested C. sinensis on animals, notes, "The swelling effect that C. sinensis has on the tissue of the penis isn't significant. If you were to rely on it to overcome impotency, I'm afraid you would have to eat a huge amount to have only a slight effect!"

The fact is that in traditional Chinese medicine, kidney-fortifying C. sinensis is thought to have no direct effect on the sexual organs. Yang Shih-fu, a Chinese herbal pharmacist, explains that fortifying the kidneys is thought to "cultivate qi." C. sinensis' effect on the sexual organs is largely indirect, by relaxing the body, cultivating qi, and dissipating tension and anxiety. If qi is flowing unhindered through the body, then sexual problems will resolve themselves. Of course, righting the overall problem requires more time. Sometimes doctors of traditional Chinese medicine prescribe both C. sinensis and animal ingredients that are packed with male hormones, such as sea horses, horned toads, deer penises and deer antlers. By so doing, they treat both the symptom and the root cause.

Viagra may have created a worldwide sensation, but from the perspective of Chinese medicine, which is opposed to sexual overindulgence, trouble with the sexual organ is indicative of overall health problems. A pill that mechanically brings about an erection instead of helping to provide a holistic solution is regarded as belonging to the category of "lower drugs," those that harm the body.The best medicine is preventive

Because C. sinensis is classified by the Department of Health as being a health food, there is no need for its manufacturers to go through the long, involved process of chemically analyzing its components, performing clinical trials and meeting other such conditions. Yet its status as a health food means that marketers of C. sinensis cannot promote its medicative or curative effects. Nevertheless, research papers published by Taiwan University Hospital and Union Chemical Laboratories report that extracts of the fungus directly stimulate the secretion of cortisone in the adrenal cortex of white mice. Cortisone is a steroid naturally produced in the human body that helps to fight allergies and infections and generally strengthens resistance to disease. But encouraging the body's own secretions is quite different from administering cortisone supplements, which might appear to be miracle workers but can easily be overused and harm the body in various ways.

"Nature is truly awe-inspiring. The Chinese herbal pharmacopeia passed down over thousands of years has many complex ingredients and effects. The more you research it, the more you feel gratitude and admiration for the wonder of creation," exclaims Yang, who holds a doctorate in chemistry.

In traditional Chinese medicine, "The best medicine is preventive." "Good drugs" are those that cultivate life and can be taken often. Chinese medicine focuses on getting one's body to gain vitality on its own, so that weaknesses are eliminated and the body can fight disease itself. As a result, in Chinese medicine different prescriptions are often used to treat the same ailment, and conversely, identical or similar prescriptions may be used to fight different diseases. For instance, according to Chinese medical principles, impotency is a symptom of 12 different possible conditions. To say that one prescription can cause all men to recover sexual potency is not regarded as possible. Even if C. sinensis is called the Chinese Viagra, it achieves its result of bolstering virility by strengthening the whole body, which gets to the crux of the difference between Chinese and Western medicine.The science of vagueness

Ancient Chinese medical texts describe the kidneys as being the root of a body's natural endowment and its source of qi, and many traditional Chinese medicines are designed to fortify the kidneys. Advertisements for kidney medicines often employ the slogan "Fortify the kidneys, maintain vitality"-as if all will be well once the kidneys are. Yang Shih-fu explains that this abundance of kidney fortifiers in these texts does not mean that ancient Chinese doctors were obsessed with the penis, because kidney fortifiers are regarded as helping not just the reproductive organs but also the urinary tract and adrenal glands. What's more, the kidneys are closely related to the bones and the lungs, and problems with breathing or the production of blood often call for prescriptions treating the kidneys.

In Chinese medicine the five Chinese primary elements (metal, wood, water, fire and earth) affect each other in various adverse or synergistic ways. In the past Chinese medicine couldn't offer any evidence in support of this theory, and Western medical doctors looked upon it as just so much nonsense. But now it is known that the cells of many organs secrete cytoplasm that affects or is even principally used by other organs. "Don't think that definitions which are vague are bad; instead you should respect the vagueness of Chinese medicine, because people are wholes that cannot be split apart. Sex has multiple functions, and the phenomenon of life is not entirely clear," asserts ICM's Chen Chieh-pu.

"In researching Chinese medicine, both developing new medicines and respecting the ancient Chinese medical principles are essential," argues Chen Chieh-pu. Synthesizing chemical components or extracting new drugs from natural herbal, mineral or animal substances has long been an important process in mainstream medicine. Quinine, which is used to treat malaria; the cardiotonic rehmannin; the painkiller morphine; and antibiotics, which are widely used and have saved so many; were all discovered in natural herbal medicines or fungi.

And even if is not now possible to analyze completely the content and methodology of traditional Chinese medical theory, many of the medicinal ingredients in its prescriptions may work in different ways to bring a patient to health, or perhaps even work synergistically to treat a disease against which they would do little or nothing individually. The US Federal Drug Administration has accepted the use of herbal drugs, and Medicare and Medicaid now cover it. "While many of its methods still defy explanation, Chinese medicine does provide an entirely different model for modern medicine and thus is a priceless asset," Chen says. "Yet the scientific method as used in Western medicine shows clearly how individual medicines work and provides Chinese medicine with effective new techniques."

Once upon a time the legendary Shen Nong tried "the 100 herbs" to begin the Chinese medical tradition. Modern day Shen Nongs needn't try 100 herbs. Instead, with the help of modern technology, they are performing compositional analysis on herbal medicines and conducting research into the theories of Chinese medicine. There is no longer such a clear-cut line between modern medicine and traditional treatments. Perhaps we await the day of an even more inspired synthesis of Western and Chinese medicine, a day when a new and better Viagra is researched and developed.