“Take two aspirin and call me in the morning” is saying that has been around for as long as we know, but let’s pause for a moment and consider what it would mean if we didn’t have access to drugs such as aspirin. Aspirin is used to treat pain, fever, inflammation, and to treat or prevent heart attacks and strokes. (There has even been preliminary data that suggests regular aspirin use can help treat/prevent cancer [1].) Prior to the 1950s there weren’t many alternatives to aspirin. So, in a world without aspirin, anything from a minor headache to a dangerous fever could not be effectively treated. Who/what can we thank for this wonder drug? The answer may surprise you: the Willow Tree.
Not having aspirin in our medical toolkit would be a big enough blow, but what if we were to also remove penicillin (the first antibiotic), anthracyclines and paclitaxel (anti-cancer drugs), digitoxin (heart failure drug), and quinine (an anti-malaria drug) from our arsenal? Given that malaria, heart disease and cancer are the leading causes of death around the globe, you can imagine that not having these drugs and those we have derived from them would be catastrophic for the human race. Just like aspirin, all of these drugs and over 214,000 [2] other compounds have been extracted from other living organisms, and this library is growing every year. These compounds are typically known as natural products and have in recent years reemerged as the main focus of pharmacologists for identifying new therapeutics (up to 30% of first-in-class drugs in recent years have been natural products) [3].
So why do we care about natural product drugs? Much like the co-evolution of the flu virus and our own cells (where both types of cells continue to participate in a metaphorical arms race to outmaneuver each other), we and many organisms have co-evolved together to a point where compounds those organisms produce for their own purposes are also biologically active in our systems. By identifying these co-evolutionary pairings we can utilize them to help us manage many diseases. From this perspective, it is fairly obvious why so many of our antibiotics have been extracted from various microbes. These organisms compete for their resources much like any other organism and it is to their benefit to produce compounds that will inhibit competing organisms from gobbling up their food. We can repurpose these compounds to help us fight off potentially deadly infections, and the uses for these compounds don’t stop at antibiotics. For example, we’ve seen potential treatments for cancer and neurodegenerative diseases come from a variety of organisms, such as bacteria and sea snails.
Why does all this matter? We are approaching a crisis in our healthcare system. The antibiotics we have are no longer as effective as they once were (due to the evolution of microbes against our use of antibiotics). History has taught us that we are far more likely to find our next powerhouse drug hiding in the trees of the rainforest, or the dirt near the Adriatic sea, than we are to find a synthetic drug in the laboratory. The kicker to this problem is that we have seen a dramatic escalation in the loss of species from this planet, and the models suggest this die-off is only going to get worse. In fact many scientists are starting to label this loss as the sixth extinction, and while it’s true that we are likely to survive a significant change in the global climate, it’s not likely true for our unknown friends, who may hold the key to preventing the next massive pandemic.
If you’d like to learn more about drug discovery and use, consider enrolling in BIOL199-001 (Introduction to Pharmacology).
- Rothwell, Peter M et al. (2012). Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomized controlled trials. The Lancet , Volume 379 , Issue 9826 , 1591 – 1601
- Ji, H.-F., Li, X.-J., & Zhang, H.-Y. (2009). Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO Reports, 10(3), 194–200.
- Eder, J., Jörg Eder, Richard Sedrani, & Christian Wiesmann. (08/01/2014). Nature reviews. drug discovery: The discovery of first-in-class drugs: Origins and evolution Nature Publishing Group.