While humans evolved over a period of about 6 million years, breakthroughs in modern medicine as we know it today only started in the 19th and 20th centuries. So how have humans successfully survived millions of years of illness and disease without modern drugs and treatments?
This was a question I asked myself when the COVID-19 pandemic reached my family in India in April 2020, when there was very limited access to vaccines and treatments. All my years of working as a biomedical scientist, requiring empirical evidence and formal safety testing before taking any treatment, I took a backseat as I looked for potential therapies from all the sources I could find, be it scientific papers or folklore. I was ready to try any experimental or traditional medicine that might have a chance to help my father.
Fortunately, my father recovered. I can’t say for sure if any of the traditional medicines we were taking really helped him recover. But as someone whose entire scientific career has focused on discovering new drugs from chemical compounds found in nature, I wondered if a molecule in the traditional drugs we used could be isolated and optimized to treat COVID- 19 to treat.
Scientists like me are looking for new drugs for various diseases by purifying existing compounds in nature instead of synthesizing completely new ones in the lab. From COVID-19 to antibiotic resistance, I believe that past successes and new technologies point to the enormous potential of developing new medicines from natural products.
The natural product advantage:
Humans have evolved along with the rest of nature over time, and obtaining medicine is arguably one of the most important interactions humans still have with the natural world. DNA analyzes have shown that early humans may have treated dental abscesses with poplar, which contains the active ingredient aspirin, and Penicillium fungus, which contains the antibiotic penicillin.
Researchers call the molecules like the ones that give poplar and Penicillium their biological effects are natural products because they are produced by living organisms such as microbes, fungi, corals and plants. These natural products have evolved to be structurally “optimized” to serve certain biological functions, primarily to deter predators or gain a survival advantage in a particular environment and over other competitors.
Since natural products are already made to function in living things, this makes them particularly attractive as a source for drug discovery. Although proteins may look different in different organisms, many have similar structural features and functions between species. This can help look for related proteins that work in humans.
Hall of fame for natural products
Natural products derived from microbes and plants are the largest source of drug discovery for modern medicine. Example: the discovery of the antibiotic penicillin in 1940 from Penicillium fungus enabled doctors to treat previously deadly infections and began the era of antibiotics.
As of September 2019, more than 50% of currently available FDA-approved medications are derived directly or indirectly from natural products. One of the best-selling drugs of the past two decades, atorvastatin (Lipitor), an anti-cholesterol drug, is derived from a compound produced by the fungus Penicillium citrinum. From 1992 to 2017, U.S. sales of atorvastatin totaled $94.67 billion.
Other prominent examples of drugs derived from natural products currently in use include the antifungal amphotericin B, isolated from the soil bacteria. Streptomyces nodosusthe chemotherapy taxol, isolated from the bark of the Pacific yew tree, and the immunosuppressive cyclosporine, isolated from the fungus Tolypocladium inflatum.
I believe that undiscovered treatments for a wide variety of diseases lie right under our noses in natural products. In January 2021, the FDA approved voclosporine (Lupkynis) isolated from the fungus Tolypocladium inflatum, to treat lupus. Recently, researchers have been exploring cannabidiol and other cannabinoid compounds as a possible way to prevent or treat COVID-19. The FDA has not yet approved a drug containing CBD for COVID-19.
Challenges in discovering natural products
Researchers are increasingly able to use new screening technologies and methods to isolate previously unidentified natural products. Screening for natural products typically involves searching a large library of extracts from natural sources. For example, the Natural Product Drug Discovery Core, which I co-founded with my colleague David Sherman at the University of Michigan, looks for potential drug targets in a library of about 50,000 natural product extracts, each containing 30 to 50 molecules for testing.
However, discovering natural-based medicines is not without its challenges. Since the 1980s, natural products have fallen out of favor due to a number of challenges. These include difficulties in accessing expensive screening methods and limitations in technology that cannot fully analyze the complexity of natural products. There are also ecological and legal considerations, such as sustainable access to samples and preserving biodiversity. Pharmaceutical companies have reduced their natural drug discovery programs, and federal funding is also scarce due to limited profitability.
Finding new medicines in nature
New drugs are often needed for unprecedented health emergencies such as COVID-19. They are also needed for a health emergency that started long before the pandemic – antibiotic resistance.
A September 2017 World Health Organization report reaffirmed that antibiotic resistance is a global health emergency that will seriously jeopardize progress in modern medicine. If current antibiotics lose their effectiveness, common medical interventions such as cesarean deliveries and cancer treatments can become incredibly risky. Transplantation can become virtually impossible. Antibiotic-resistant microbes were the direct cause of approximately 1.27 million deaths in 2019. In the US alone, treating just six of the 18 microbes that threaten antibiotic resistance costs more than $4.6 billion annually. The COVID-19 pandemic has reversed previous progress in addressing this problem, with antimicrobial-resistant infections increasing by 15% from 2019 to 2020. In contrast, antimicrobial-resistant infections had fallen by 27% from 2012 to 2017. One of the probable causes of this relapse were an increase in antibiotic use, difficulty following infection control guidelines, and longer hospital stays.
According to recent estimates, about 75% of approved antibiotics come from natural products. There are still thousands of microorganisms in the ocean to explore as potential sources of drug candidates, not to mention all of them on land. In the search for new drugs to combat antibiotic resistance, natural products can still be the best choice.