neem

Innovation in medicines: inspiration comes from nature

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Morphine and codeine painkillers, taxol (anticancer), artemisinin (antimalarial) or aspirin... All these drugs have the particularity of having been discovered in plants or being derived from them. In fact, even today, as for millennia, the environment still provides us with most of the compounds that enable us to treat ourselves.

Po identify new drugs within traditional pharmacopoeias, which give pride of place to natural substances, ethnopharmacologists are at work.

Birth of pharmacology

At the beginning of the 19th centurye In the 19th century, scientists became passionate about a new discipline, pharmacognosy (etymologically "knowledge of medicine"). The aim is to identify and isolate the active ingredients contained in raw materials of biological or mineral origin used in "traditional" medicine. Pharmacognosy is particularly interested in the plants used in popular pharmacopoeias.

At that time, thanks to advances in chemistry, the pace of discovery of new drug substances by chemical pharmacists was accelerating. Morphine was isolated from the sleeping poppy in 1804, emetin, a potent emetic, was discovered in the South American shrub ipecac in 1817, and strychnine was extracted from the vomit nut in 1818. Then came the famous quinine in 1820 (an anti-malarial drug derived from cinchona, another South American shrub), salicylic acid extracted from the willow tree in 1828 (which would be used to create aspirin), or codeine, a pain reliever isolated in 1832 in the poppy...

Sleeping poppy is the source of two powerful analgesics, morphine and codeine. Shutterstock

The discoveries of these active ingredients, which were inspired by traditional medicinal knowledge, then opened up a new field of research: pharmacology. The focus is now on the mechanisms of action of drugs, and how to improve them.

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Major pharmaceutical groups were born at this time: Pfizer was founded in 1849, Bayer and Hoerst in 1863.

From natural to artificial

In the 1930s, chemists developed the first methods of artificially manufacturing chemical compounds. These soon replaced a large proportion of naturally occurring drugs, which are much more expensive and time-consuming for industry to produce. Gradually, plant drugs were dethroned: their number increased from 820 in the Codex of 1818 to 207 in the Codex of 1918.1949 edition.

To meet the search for efficiency and profitability, new technologies were developed, such as high throughput screening, in the 1980s. This automated technique makes it possible to rapidly test the effect of several thousand molecules on a therapeutic target (cancer cells, infectious bacteria, etc.). The combination of this method with another recent discipline, combinatorial chemistry (which makes it possible to rapidly manufacture thousands of molecules that differ slightly from one another), should have led to a pharmaceutical revolution.

But things didn't go as planned...

Nature, champion of originality

The success of these new tools finally turned out to be relative Today, most of the "new" drugs on the market today are just "new" drugs. reformulations of already marketed products.

This mixed success can be explained in particular by the fact that combinatorial chemistry generates only certain kinds of molecules. So the diversity is much less than the one found in the environment. On the other hand, nature is sometimes capable of prowess that chemists can only reproduce at great expense, as in the case of the taxol.

The environment therefore remains a privileged source for the identification of completely innovative active ingredients: more than half of all medicines are still today, derived more or less directly from natural resources.

The toxicity of the common yew, from which the anti-cancer drug taxol is derived, has been known since antiquity.

In this context ethnopharmacologists have an important role to play. Indeed, the contributions of traditional knowledge is crucial in the process that will lead to the discovery of new active ingredients. Their mission is precisely to meet with populations to identify, with their consent, the therapeutic uses and associated species. Once the practices are known, their effectiveness must be evaluated. Finally, if the activity of a remedy is proven and its active principle identified, and if we have the financial means, we can consider using it to develop new medicines.

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The work of ethnopharmacologists therefore allows a first selection to be made among the countless species of biodiversity, selecting those with strong potential. Provided that certain rules are respected.

 

Valorize without plundering

In recent years, this ethnopharmacological approach has become considerably more complicated for investors, whether public bodies or pharmaceutical companies, due to new regulations. This complexity has been compounded for the right reason: for a long time, it was possible to file patents based on traditional knowledge without worrying about the possible benefits for the populations that inspired them, which did not receive any profit.

This was particularly the case for the Neema medicinal plant used in India for generations for its antifungal properties, the Hoodiaa well-known appetite suppressant for the Bushmen in South Africa, or the Maca from Peru, sought after for its aphrodisiac virtues.

In order to combat this biopiracy, the Nagoya Protocol has been established, within the framework of the Convention on Biological Diversity. Entering into force in 2014 and signed by 105 States, it defines a regulatory context for access to genetic resources such as plants, animals, bacteria or other organisms. It provides for the fair and equitable sharing of the benefits arising from the use of these resources. The protocol also covers traditional knowledge. While access to resources has become less easy, these provisions nevertheless seem beneficial.

The positive effects of the Nagoya protocol

The Nagoya Protocol aims to ensure the ethical and sustainable use of the countries' natural resources, i.e. respectful of communities holding traditional knowledge and their environment.

Recent cases have demonstrated the positive impact of its implementation, as patent applications are re-examined from another angle, with a new opportunity for both the patent holders and the indigenous communities that contributed to the discovery to valorise their traditional knowledge.

As proof of the importance of this knowledge, since 1978 and the declaration of Alma-Ata, the WHO has been recommending the study of traditional medicines and the integration of proven effective remedies into the conventional therapeutic arsenal. Ethnopharmacologists are not yet retired....

Elodie DranéPhD student, University of the West Indies

Header image: Neem (Azadirachta indica), known in India for its antifungal properties.

The original text of this article was published on The Conversation.

 

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