You may not realise it, but many of the medicines sold in pharmacies are either directly sourced from nature or have an underlying operating principle drawn from a natural process. Widely used pain relievers paracetamol and aspirin? Originally derived from coal tar and willow bark, respectively. Cholesterol-lowering statins or morphine-like pain medicines? From bacterial fermentation broth and poppy plants. While these can now be synthesised, i.e., created by chemical methods in the laboratory, many drugs have never been successfully synthesised or where the total synthesis is too arduous or expensive to utilise in mass production. Instead, natural products are often used as starting points in so-called semisynthetic production.

     As for those medicines that have no natural source but are instead completely synthetic, they are often based on or discovered through chemical processes that humans have observed in nature. Natural processes are the greatest source of pharmaceutical knowledge known to modern medicine. It is certainly not a coincidence that the Golden Age of drug discovery coincided with the Industrial Revolution. Industrial practices standardised and optimised medicinal research, development, and production to be used en masse. The fossil fuel industry quickly developed side branches in the so-called petrochemical industries. Petrochemicals are chemical products obtained from petroleum refinements, such as solvents used to synthesise and extract natural products from plant leaves, barks, and other sources. These solvents and methods considerably increased the extraction and characterisation (i.e., chemical identification and description) of medically useful natural compounds. The growth of modern medicine coincides entirely with the industrial usage of fossil fuels.

     At the same time, human industrial activity has had a considerable impact on the Earth, to the point where a new name for our geological age, “the Anthropocene,” has been proposed. The ability to use energy very efficiently to modify the environment is a hallmark of industrial society. This includes intentional use, e.g., around half of the Earth’s habitable land area is currently used for agriculture, and unintended side effects, such as environmental microplastics and climate change. It may be hard to completely decouple the negative environmental repercussions from the positive effects of economic expansion, but it is evident that human-caused environmental changes must be considered to a greater extent.

     Many currently used antibiotics are derived from soil microorganisms, but it has been estimated that less than 1% of microbes have been researched. This is partly due to many of them not being easily cultivated in laboratory conditions or not necessarily producing the same “interesting” chemicals there as they do in the wild. Meanwhile, human industrial food manufacture threatens soil biodiversity and contaminates the environment with antimicrobial residue. It is currently estimated that about 75% of all the produced antibiotics are used in agriculture, especially as growth promoters in animal husbandry.[i] This excessive use of antimicrobials causes drug resistance to accumulate in bacteria across the food chain and in human populations.

     Agriculture’s spread, one of humanity’s most significant environmental impacts, has also changed wildlife habitats and has become one of the biggest threats to biodiversity and soil quality[ii]. Biodiversity loss will probably affect many people’s health around the world in unexpected ways. While most people in industrial cultures buy ready-made medicinal items from pharmacies and hospitals, traditional natural product remedies are commonly used in other parts of the world. In India and China, it is estimated that natural product cures are used by 80-95 percent of the population. Climate change and environmental erosion will cause not only difficulties in harvesting certain plants but will also cause changes amounts of medicinal compounds in them.

     Another separate issue is whether the extinction of species and dramatic changes in ecosystems will lead to a loss of opportunities to discover new drugs and other bioactive compounds. This is a difficult question to answer as there is no comprehensive understanding of how many bioactive compounds exist out there and in which parts of nature they are more likely to be. Plants and microbes have competed with parasites and pests for millions of years and are therefore likely to contain antibiotics, cancer-inhibiting chemicals, or nervous system poisons[iii]. But options for other treatments and diseases, such as in the case of rare genetic defects, are likely fewer. And while nature does produce more complex structures than most human-made compounds, there is also much redundancy. Many variations of the same themes are present within individual organisms and in between different kinds of organisms. This makes it laborious to sieve out the rare golden nuggets. It has also been suggested that the “low hanging fruits” of natural drugs have already been picked, and those medicinal compounds with the clearest and strongest effects have already been discovered by modern medicine. In fact, most of them were already known when modern medicine started to work on them. Systematically screening plants and other organisms looking for less obvious but useful bio tools is very laborious, requiring many kinds of special expertise. The material must be harvested or cultured, the compounds extracted and characterised, and their activity assessed in panels of assays.

     However, there are numerous areas of nature where there has been minimal, if any, search for bioactives. The vast majority of microorganisms on the planet are difficult to cultivate in the lab, and many ecosystems remain largely uncharacterised. Deep-sea biology is very much an unknown. Furthermore, it’s possible that drug-like compounds are not evenly distributed across all natural habitats and that projections based on present studies can’t accurately forecast the entire picture. Some drug-like molecules may even be present in existing laboratory samples, in extremely small quantities or under rare conditions. Academic researchers are increasingly tinkering with the genomes of microbes and other species in the hopes of expressing so-called cryptic natural products, molecules produced only in unusual circumstances, such as the presence of other specific organisms. And others have begun to move gene clusters to facilitate the growth of laboratory strains, increasing the yields of compounds that only appear in extremely low concentrations in the wild or to edit the genomes in ways to improve current systems.  

     The Anthropocene is not just an epoch in which human actions have a large-scale impact on the environment; these acts also have a profound impact on human-nature connections. Because cities now house more than half of the world’s population, many traditional societies and their knowledge are becoming extinct. It is anticipated that 30 percent of the world’s approximately 7000 languages will become extinct before the next century. The vast majority of all folk medicinal traditions have never been studied in detail, and it is possible that entire health care systems will disappear before they are studied. This disappearance of folk knowledge is more severe than the extinction of wild organisms since the effect seems to be more widespread and happening at a quicker pace. A vast amount of Ethnopharmacology studies have been conducted, but most of these are performed on written collections of traditional healing methods, as these are easy to access in already printed and digitised versions. These issues cannot be solved by focusing alone on chemistry, biosciences, or policy management; rather, they will necessitate collaborative efforts from all of these sectors.

     Climate change, habitat loss, and species extinction are major and complicated issues emerging from an industrial lifestyle. It is clear that much innovation has been derived from natural processes and that we would greatly benefit from having this source of inspiration in the forthcoming decades and centuries. Sustainability is now widely accepted to be an essential requirement for the future of humanity, and here is yet another reason for this: to ensure the continuing benefit to human health by means of drug development.

REFERENCES

[1] https://www.farmprogress.com/story-soil-microbes-human-health-dont-know-9-131505
https://www.annualreviews.org/doi/10.1146/annurev-micro-090816-093449?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638249/
[3] of the 28,000 species designated as threatened with extinction on the IUCN Red List, agriculture poses a hazard to 24,000 of them. Agriculture also has strong effects on soil quality. https://globalchallenges.ch/issue/6/soil-degradation-at-the-core-of-the-anthropocenes-intricate-fragility/
[4] These are all in essence some form of “poison”, since cancer-inhibiting drugs are cell poisons, antibiotics are bacteria killing poisons, and drugs affecting the mind are nervous system poisons.