A New Paradigm In Bioprospecting
Plant matter accounts for over 19,000 chemicals in use today, and the number is accelerating. In the field of biochemicals, enormous sums are being spent on plant research for the creation of products ranging from industrial solvents, to plastics, printing ink and adhesives. The cosmetic industry, taking advantage of a general trend toward a more natural lifestyle, have turned to the plant world for skin softeners, toners and bleaches. Food companies are using plant molecules for adding flavor and texture to processed foods. Dyes for clothing and decoration are increasingly plant based.
In nearly every aspect of life we see research into plant compounds gaining momentum, yet, in the field of medicine, the growth rate in the use of plant molecules has stagnated, in spite of the fact that medicines derived from plants, and used historically, make up a large part of a doctor’s arsenal. Penicillin and Streptomycin are two examples of older drugs with widespread current use, both being obtained from fungi. But, with the notable exception of Madecassol (an extraction of Centella asiatica used to treat burns), no major drug based exclusively on plant compounds has been produced for the past 25 years. In general, synthetic drugs are cheaper to make. They are manufactured on a mass production basis, with less labor. They do not impose a reliance on plants from foreign lands or on rare minerals. But more importantly, synthetic drugs can be patented. A patent locks out competition and allows the patent owner to control the market for the drug. This is a large motivating factor when choosing a path for medicinal research.
The above is not to say that research into the pharmacological properties of medicinal plants has stopped. On the contrary, in the field of antibiotics there has recently been a huge push in the direction of plant research. Our antibiotic arsenal is nearing the end of its useful life and synthetic approaches are yielding fewer and fewer results. Nearly every major drug manufacturer has extensive programs in place to look for antibiotic properties within the natural world. Yet, in spite of the push toward plant research, No major class of plant compounds has been discovered that shows much promise. It appears that the chemical means of killing bacteria using plant compounds, mirroring the results of synthetic approaches, is nearing exhaustion.
At QuorumEx, we believe that the reason antibiotic properties have not been found in many of these laboratory tests is because science has been following a dead end approach to researching the problem. The discovery of the first antibiotic, which acted by outright killing of bacteria, led research in the direction of identifying more substances that killed bacteria. One problem with this approach has been that any mutations in the bacterial colonies that were, by chance, immune to the antibiotic were the only individuals left alive to propagate and multiply. These individuals did not have to compete with the billions of original bacteria that were killed off. Thus new strains, immune to the antibiotic, developed and spread.
A second problem with this approach is that, for decades, these antibacterial compounds were effective, and there appeared no need to question whether a different paradigm for the control of bacteria existed. So the search for new antibacterials has been narrowly focused.
Laboratory methods for identifying potential antibiotic compounds within the plant world have used a brute force approach. Tens of thousands of plant extracts have been tested for compounds capable of killing bacteria in a laboratory. If this in vitro testing proved promising, then in vivo studies commenced with animal and eventually human subjects. If, on the other hand, the compound was found to be ineffective at killing bacteria in vitro, it was discarded.
Frequently, plants that had a long history of medicinal use by indigenous peoples, and sound anthropological evidence of effectiveness, were included as priority substances for this in vitro testing. Yet, even when inescapable anthropological and anecdotal evidence existed for a plant’s effectiveness against bacteria, if the plant was found unable to kill bacteria in vitro, then it was entirely discounted. This schism between anthropological evidence and scientific laboratory research into antibacterials has been one of the main factors that have created a view of traditional plant medicines as inferior, imprecise, ineffective or based purely on the placebo effect.
The New Paradigm
New discoveries about the way that bacteria behave in collective environments have changed the playing field. Anti quorum sensing compounds using qs signaling molecules that control infection, work without killing the bacteria. They instead control the bacteria’s ability to communicate with other bacteria. In vitro studies in a large number of scientific tests have shown a high degree of effectiveness of these compounds in preventing pathogenesis. In vivo studies using plant derived compounds at QuorumEx have gone beyond the lab, and have shown astonishing success at preventing infection in human subjects. Yet these compounds could have been present in many past scientific tests, and would have been discarded.
Plant based medicinal research at QuorumEx involves aspects of biological, medical, cultural and pharmaceutical sciences. We are concerned with the discovery, design, identification, and preparation of biologically active compounds from plants. We focus on plant metabolism, the interpretation of plant processes at the molecular level, and the construction of structure-activity relationships. We are not simply looking for a hammer to smash bacteria.