Attitudes toward the use of plants in medical treatments have taken a cyclical swing over the past two hundred years. Prior to the 19 th century herbal remedies were commonplace, effective and subject to neither ridicule nor skepticism. No one queried their efficacy, as the evidence upon which their use was based was consistent, globally, over time and place, since the beginning of recorded history. Then, in the early part of the nineteenth century extraction of active plant constituents that proved to be therapeutically effective in the treatment of specific diseases heralded the birth of modern pharmacology. The Herb Spiral probes some of the history of this scientific process, how it evolved from the pursuit of a magical cure for every malaise, the rise of the drug industry whose vested interests demand the discrediting of the very medicine that was in fact its precursor, its beginning, to a growing appreciation that the effectiveness of medicinal plants cannot always be reduced to that of a single extracted constituent.

Early experiments in what has became the science of pharmacology were carried out by a number of French scientists, and in 1803 Charles Derosne extracted a mixture of 2 alkaloids from opium . Then in 1817, Friedrich Wilhelm Adam Sertürner who was purifying constituents from opium succeeded in isolating morphine.* At that time another alkaloid isolated was quinine, from the South American cinchona tree, and would later become an antimalarial drug that would provide a profound and lasting benefit to the health of African and other tropical populations

During the 19 th century the process of isolating principles from plants was actively pursued and in 1821 the renowned French s cientist François Magendie published a pocket book entitled “Formulary for the preparation and use of several new drugs, such as nux vomica, morphine, prussic acid, strychinine, veratrine, the cinchona alkaloids, emetine, iodine. * This work became an essential guide to the use of isolated alkaloids in clinical medicine

The foundations of pharmacology were thus laid as the isolation and purification of constituents from plant medicines, which had already been used in various non-purified forms. * In fact, about half of the pharmaceutical medicines at the beginning of the 20 th century were still “impure” multi-constituent plant medicines. * Many of the 19 th century and early 20 th century medical journals documented case studies substantiating the effectiveness of plant medicines in their crude form.

Much work was carried out in the nineteenth century based upon observations of response of living systems exposed to substances, organic and inorganic. This focus produced drugs such as aspirin from combining acetyl chloride with sodium salicylate, penicillin from fungi and the anticancer drug cisplatin from an inorganic potassium salt.

Successes from the isolation and purification of active constituents from plants are undeniable, and it is argued that these products afford the advantage of precise dosing and decreases the possible adverse events induced by other plant constituents. However these compounds clearly have their own risks.

A 2006 report of the Institute of Medicine puts the number of medication errors causing injury to Americans at 1.5 million per year, a remarkable statistic taking into account that reports of adverse events are estimated to be underreported by a factor of 10* * Furthermore, the British Medical Journal noted that adverse events from herbal remedies are “a tiny fraction of adverse events associated with conventional drugs,” and risks

Moreover, the notion that “therapeutic reproducibility” is better because of the ability to offer more precise dosing of an isolated chemical totally ignores the wide variation in drug metabolism in individuals which can vary at least 60-fold in healthy subjects. * Therefore, if an individual with a slow metabolism is exposed to a concentrated chemical, severe toxicity may occur whereas the probability of this occurring with a medicinal plant, which is inherently a dilute mixture of chemicals, is, relatively speaking, significantly less. *

Another argument regularly heard is that the low concentration of any one constituent in a plant creates a mixture of compounds too dilute to have any beneficial effect. In fact, it has been shown that even very low concentrations of any one chemical will contribute to the chemical mixture's activity, even if that chemical does not show activity when isolated. * As early as 1928 it was demonstrated that the effectiveness of combinations of constituents was different to that which might predicted by the activity of the isolated constituents. * That is to say that the therapeutic benefit of a medicinal plant often cannot be reduced to that of any single constituent.

It is, indeed, rare that a medicinal plant has only one bioactive constituent. * * In fact, medicinal plants commonly contain numerous active constituents. It has been shown that the componenets of a single plant can have complementary and overlapping effects on human physiology, including anti-inflammatory effects, stimulation of the immune system, hormone metabolism, and antimicrobial effects. *

Sweet wormwood, also known as Sweet Annie, source of the antimalarial drug artemesinin, contains a variety of antimalarial constituents.Similarly, Madagascar periwinkle from which the cancer drugs vincristine and vinblastine are derived, contains close to 100 distinct alkaloids. *

A recent study done with a mixture of the three alkaloids—quinine, quinidine, and cinchonine—demonstrated a synergic effect against a culture of P. falciparum, * the most deadly of malaria parasites. Additionally, the Plasmodium strains that were resistant to quinine were up to 10 times more susceptible to the alkaloid mixture than any one of the single alkaloids. It is possible that Plasmodium resistance could be at least delayed, if not avoided, with prudent use of such therapeutic mixtures.

The strategy of using multiple compounds in clinical medicine is already in use. Drug cocktails have had success in the treatment of other complex diseases. For example, treatments for cancer, infectious diseases and hypertension, and psychiatric treatment protocols are achieving maximum benefit by targeting several biochemical pathways simultaneously; exploiting synergy, and minimizing toxicity. * Drug cocktails are being used to compensate for resistance in tuberculosis found in the inner cities. Also, drug cocktail therapies are having successful outcomes in the treatment of AIDS and bacterial, fungal, and viral infections.

Thus, the search for compounds with high affinity and selectivity, which has dominated pharmacological research, may not necessarily be as effective for alteration of a cellular network. * as low-affinity multi-target drugs such as plant extracts. The position of the United Nations Convention on Biological Diversity is that evolution has been selecting and perfecting diverse bioactive molecules for millions of years. * Hopefully, then, workers in the science of pharmacology will recognize this premise in their choices of the directions that their research will take them in future years. Research may best be targeted, not at expensively manufactured and marketed silver bullets hitting a single target, but as multi-component, broad-spectrum, molecular cocktails.

Ian Finlayson