A video on Facebook with聽聽informs me that the avocado tree is a pharmacy in disguise. 鈥淚ts leaves help regulate blood sugar,鈥� the narrator says, 鈥渋ts seeds target cancer cells, and its bitter compounds are being studied for their effects on infections.鈥�
It鈥檚 appealing to think of Mother Nature hiding every cure we will ever need in plain sight. One of the core messages of alternative medicine is that stuff found in nature must be good and safe, while artificial compounds are necessarily dubious, if not outright poisonous. I guess its marketing team forgot about snake venom, asbestos, and poison ivy.
But just because a molecule isolated from a leaf or root or fruit has some interesting property does not mean it鈥檚 a science-based drug from the garden of Eden.
In fact, it rarely pans out in the long run. Why is that?
The low-hanging fruit
Science is hard. I don鈥檛 mean this as a thought-terminating clich茅, but rather as the correct frame when discussing our efforts to understand the universe around us and to derive benefits from this understanding. When we forage for drugs in our backyard, we must understand that the payoff will not be imminent.
Part of the reason is that we鈥檙e walking in a field that鈥檚 already been picked. The low-hanging fruit has been in our pharmacies for a while. The first plant-derived compound used as a drug was morphine, isolated from the opium poppy in聽, and our species has gone on to use chemistry to extract useful molecules from trees and bushes, compounds like caffeine, quinine, and taxol. Whatever is left to find will necessarily be harder to spot.
While we look for medically useful molecules around us, we can鈥檛 actually destroy nature in the process. The Convention on Biological Diversity, for instance, which was signed in 1992, helps prevent the exploitation of plant and animal species, as well as microorganisms: restrictions like this can make the source of a potential drug聽. Thankfully, we no longer need to rely exclusively on nature; we can often synthesize a natural molecule in the laboratory.
And it is important not to get stuck on the false choice between natural and artificial molecules. Whether vitamin C is found in a bell pepper or made in the lab, the molecule is identical. In fact,聽improving聽on nature has saved us from a few pains along the way. You may have heard that the active ingredient in Aspirin, acetylsalicylic acid, comes from the bark of the willow tree; but actually, it鈥檚 a related molecule, salicin, that was found in that bark. Salicin irritates the stomach, so one of Bayer鈥檚 chemists modified it and acetylsalicylic acid was born.
We must thus resist the appeal to nature鈥攖hat everything found in the natural world is necessarily good and safe鈥攂ecause plants are not mere medicine manufacturers; they produce compounds meant to protect them from predators. Sure, some of them may have interesting properties in humans, but others are simply toxic to us (keeping in mind that it鈥檚 the dose that makes the poison).
We are not giant Petri dishes
When a natural compound is introduced inside of a piece of plastic in the lab where individual cells grow, scientists will often see something interesting happen, and these preliminary findings are often used to market the plant to an eager audience. Natural compounds are said to have anticancer activity, or antibacterial activity, or anti-inflammatory activity. It鈥檚 true. In artificial conditions, when a large dose of some natural compound is repeatedly dropped on top of cells that have been plucked from the human body, they do cause interesting changes. But that鈥檚 a little bit like choosing a child who has just learned to ride his tricycle and immediately putting them in the driver鈥檚 seat of an eighteen-wheeler to drive cross-country. Driving in the real world is a little bit more complicated than this.
A natural compound with interesting properties聽in vitro聽must check a long list of boxes before it can be accepted as a safe and effective drug for humans to take. First of all, it has to be found. If we鈥檙e basing our interest on the ancient practice of an herb curing an ailment, we have to find the one molecule among hundreds inside the herb that carries this alleged healing activity. (This can be difficult as so many plants are rumoured to be cure-alls. If something is said to cure everything, it often cures nothing.) We also have to remove from the plant any molecule that is toxic to us. And once we have our compound of interest, we need to make sure we are testing identical doses of it. A team once tested聽聽on human participants, and they required multiple bottles of the stuff from the same manufacturer. The only problem was that the manufacturer鈥檚 extract varied from batch to batch, because the grapes came from different farms with different soils and were harvested under different weather conditions. Plants are living things, and the amounts of compounds they produce change with their environment.
Perhaps the greatest challenge comes from ensuring that this compound will reach its target inside the body in a large enough amount. The bioavailability of a drug is how much of what was given to the patient ends up in the blood to reach various parts of the body. It鈥檚 easy for our tricycle enthusiast to reach the end of the driveway but driving across the country is the real challenge: likewise, it鈥檚 simple to spray cells with a natural compound, but when you take it by mouth, will it reach those cells inside your body that need it? Will it survive the enzyme in our saliva, the acid in our stomach, the metabolism of our liver?
Testing these compounds in an actual organism, like a mouse or rat, is a step in the right direction, but even when the test is successful, the molecule often does not achieve the same benefit in humans: after all, though we share a large percentage of our genes with them, we are not giant rats.
A fraction I have often used to recalibrate people鈥檚 perceptions of drug development is 1 in 10. A decade ago, a聽聽was published in聽Nature Biotechnology聽that bore a downbeat subtitle: 鈥淭he most comprehensive survey of clinical success rates across the drug industry to date shows productivity may be even lower than previous estimates.鈥� At the time, nine out of every ten drugs that looked really promising in animal models and that received the go-ahead to be tested in humans did not traverse this gauntlet. They were not approved. Only one out of every ten promising compounds managed to show enough benefits and safety in humans that they could be prescribed. Again, we are not giant rats. As these compounds get pushed through the obstacle course of聽in vitro聽studies, animal studies, and clinical trials, we must expect a lot of failure and only the occasional success.
Bypassing the gauntlet
So, what is a natural health enthusiast to do with promising preliminary results and the high chance of a failure? Why, bypass the drug development process and sell the compound as a 鈥渄ietary supplement鈥� (in the United States) or a 鈥渘atural health product鈥� (in Canada)! The bar for approval is much lower, and the vague claims you can stick on the packaging (like 鈥渉elps promote healthy blood pressure levels鈥�) will convince the average consumer that what they鈥檙e getting has been shown to work.
And that is why so many natural compounds end up getting sold not as drugs but as supplements. The lack of proper regulation, combined with consumers鈥� appetite and the desire to keep costs down, leads to many of these herbal supplements to be adulterated鈥攎eaning that the ground-up herb you think you鈥檙e getting is actually a different herb, often cheaper to obtain鈥攐r contaminated with something else that shouldn鈥檛 be there. Allergic reactions and liver and kidney toxicity聽can follow.
Nature continues to inspire researchers and there is no doubt that its molecules will continue to transition to the clinic after a rigorous vetting process. But we should not recommend that cancer patients eat an avocado a day just because a compound found in avocados kills cancer cells in a Petri dish. After all, as聽聽illustrates, a handgun does the same thing.
Take-home message:
- Natural medicine enthusiasts will often refer to nature as a pharmacy in disguise and claim that various herbs, trees, seeds, fruits, roots, and leaves have healing properties
- The fact that a natural molecule has some anticancer activity when added to cells in a plastic dish does not mean it will be safe and effective when given to a patient; in fact, most of these promising compounds fail when rigorously tested in humans
