We’ve been using plants as medicines for a long time. Longer than history — hollyhock has been found in the graves of Neanderthals, and yarrow and chamomile have been found on their teeth [1]. Longer indeed than humanity itself — many animals self-medicate, including chimpanzees, monkeys, baboons and lemurs [2]. A long time.
Plants are full of antimicrobial compounds [3] . They lack an adaptive immune system, and so depend on chemicals to protect them from bacterial pathogens. Here’s the beginning of a list of plant antimicrobial compounds:
From Plant Products as Antimicrobial Agents
That’s just the A’s and the B’s. It’s a long list.
Roughly 2/3rds of all modern medicines are derived from natural compounds. Most of these are from plants. They treat all kinds of maladies, from pain to gout to heart disease to cancer. And yet not a single modern antimicrobial is plant-derived, despite the fact that plants are loaded with them. Instead, nearly all antimicrobials have bacterial and fungal origins. That seems more than a little odd, and calls out for some sort of explanation.
At the risk of telling a just-so story, here’s my hypothesis:
- Plant antimicrobials work internally; fungal and bacterial antimicrobials work externally.
A consequence of this dichotomy is that even small amounts of plant antimicrobials will be present at high effective concentration. Bacterial and fungal compounds, by contrast, will diffuse into the environment. Their concentrations fall with the cube of distance.
Bacterial and fungal antimicrobials have to be highly potent, because bacteria and fungi are small (they can’t make a lot) and their antimicrobial concentrations are never high. The prediction (well, actually a post-diction, I already knew this) is that plant antimicrobials will tend to be much less potent than bacterial and fungal antimicrobials.
Allicin, found in garlic and onions, is a good example. We typically measure the potency of antibiotics by their Minimal Inhibitory Concentration. The MIC50 is the concentration that will inhibit the growth of 50% of a set of bacterial strains being tested. Lower numbers (less drug) are better. Here’s how allicin compares to some modern antibiotics against Staphylococcus aureus:
Cefazolin and oxacillin are ß-lactams derived from fungal compounds.
Most clinically useful antibiotics have MIC values on the order of 1 µg/ml. Most plant antimicrobials have MIC values 10–1000 fold higher. That’s not good enough to make them clinically useful.
Another consequence of the internal/external dichotomy is that plants can employ several antimicrobials in combination. No single one may be very effective, but together they have multiplicative effects, and broaden the range of bacteria that they work against. This synergistic effect may work well in the internal environment of the plant, but would be harder to implement in soil or water.
Or to develop into a modern pharmaceutical. Getting several different compounds all absorbed and distributed and present at the right concentrations would be a nightmare for drug development. I would fire anyone who pitched such a project.
The ancients, who knew lots about plants, lacked one more critical piece of information – germ theory. Is that cough bacterial or viral pneumonia? How about TB? Or is it irritation from cooking in a smoky hut for decades? Or is it lung cancer? Without germ theory, matching the medicine to the infection was almost impossible.
And in any case, saving lives was not the point of ancient medicine. Once agriculture arrived, there were always more people than could be fed satisfactorily. More mouths were not needed. Medicines relieved suffering – often through the placebo effect – and strengthened social bonds. Potent cures of infectious disease would have simply increased deaths from starvation. Medicine – now and in the past – is primarily a social technology.
Footnotes
[1] Evidence for the Paleoethnobotany of the Neanderthal: A Review of the Literature