In 1846, a patient with a tumor in their neck decided to be the first to try something that must have seemed radical, perhaps even desperate: anesthesia. Inhaling ether gas before going under the knife, that gamble paid off in spades. To undergo surgery today without anesthesia is inconceivable.

The idea, however, was not new, even in 1846. It had been proposed 28 years earlier by none other than Michael Faraday, now famous for his work on electromagnetic fields and for the invention of the magical Faraday cage, which protects occupants from lightning or other large, unfortunate bursts of electricity (If you've never seen one of these in operation at a science museum, it is definitely worth a trip).

Yet for a concept that is nearly 200 years old, anesthesia has proved shockingly resistant to probing. We still do not understand how it works, or why so many structurally unrelated chemicals – diethyl ether, chloroform, halothane, isoflurane, and even the inert noble gas xenon – all knock out animals equally well.

What is perhaps even more startling is that this exact same odd group of chemicals works on not just animals, but also plants. You can put a Venus flytrap to sleep as easily as the fruit fly hovering above it.

Here is the standard flytrap in action. Triggering hairs in its trap twice within a short period causes it to snap shut.

Credit: Yokawa et al. 2017

But when exposed to diethyl ether gas, the plant slumbers.

Credit: Yokawa et al. 2017

Although this was news to me and presumably also to you, scientists have actually known for some time that plants are as susceptible to anesthesia as we are. Claude Bernard showed the sensitive plant, Mimosa pudica, succumbed to it as early as 1878.

Here, a normal sensitive plant reacts to touch:

Credit: Yokawa et al. 2017

And here, an anesthetized one.

Credit: Yokawa et al. 2017

But the mystery runs deeper: incredibly, not just animals and plants, but every organism on the planet can be anesthetized. Bacteria, chloroplasts, and even the very mitochondria inside our cells are affected by these mysterious gasses.

Plants, however, may provide a unique experimental opportunity. Recently, a team of scientists from Germany, Japan, the Czech Republic, and Italy wondered if, perhaps, studying plants might be key to cracking the mystery of how anesthesia works, not only in them, but in us. They published their results in December in the Annals of Botany.

First, they showed that more plants were susceptible to the effects of anaesthesia than had been known. In addition to the Venus flytrap and the sensitive plant (Mimosa pudica), cape sundew, whose sticky leaves curl around insects trapped upon them, and pea tendrils, which normally move in slow, probing revolutions, also froze when gassed.

They also tried applying a local anaesthetic – lidocaine, a chemical that your dentist might use – to the roots of the sensitive plant. This, too, paralyzed the plant about five hours after the anesthetic was applied.

There are two major schools of thought on how anesthesia works. The first posits that anesthetics bind to some sort of receptor. A receptor is exactly what it sounds like: a molecule with a pocket whose shape happens to fit those of anesthesia chemicals. By binding to this pocket, called an active site, anesthetics would work by causing a change in the shape of the receptor that sets in motion a chemical cascade leading to loss of motion and, in humans, consciousness.

The second camp suggests anesthetics work by altering the cell membrane. The cell membrane a double layer of biochemicals called phospholipids. The phospholipid layers form mirror image oceans in which membrane proteins float like wayward islands.

Cell membrane detailed diagram en.svg
Credit: Marina Ruiz Wikimedia

Many of the membrane proteins act as gated portals, controlling the traffic of biochemicals into and out of the cell. In this way, the membrane maintains the electrical charge of the cell with respect to its environment by blocking the passage of ions -- small charged atoms or molecules -- unless they pass through the appropriate gates.

This function is vital to cells that transmit nerve signals in animals because charge differences between the inside and outside of the cell propagate action potentials. An action potential is an electrical pulse. Ion portals in the membrane rapidly open and close, changing the charge in a heartbeat.

Action potential.svg
Credit: Chris 73 Wikimedia (CC-by-3.0)

In an animal, the cells that generate action potentials are neurons, the smallest units of the nervous system. The action potential is passed down the axon -- basically, the wire -- of a neuron in a wave as successive ion portals open and close.

Action Potential.gif
Credit: Laurentaylorj Wikimedia (CC BY-SA 3.0)

This is material to our discussion of anesthesia because however it is that anesthesia starts its work, the end result is the loss of action potentials. When anesthesia takes hold of an animal, the neuronal heartbeat vanishes.

Plants, too, can generate action potentials. In the Venus flytrap, the cells that generate action potentials are the trigger cells at the base of the trap hairs.

And what these scientists, importantly, have shown, is that anesthesia silences the action potentials of the Venus flytrap as sure as it does ours.

Appropriately enough, they placed their Venus flytraps inside Faraday cages in order to monitor their action potentials. Under the influence of diethyl ether gas, the same anesthetic used in that first surgery back in 1846, the trigger cell action potentials vanished, then slowly recovered after the gas was removed.

Action potentials in Venus flytraps exposed or not exposed to anethesia, and their recovery in seconds after anesthetic removal. Credit: Yokawa et al. 2017

This suggests, somewhat grandly, that bioelectricity and action potentials power the motions of plants and animals alike. That two groups separated by such a profound evolutionary gulf share the same drive train hints at a deeper biological truth surrounding how Venus flytraps count and other signs of plant intelligence.

The scientists also conducted experiments designed to test the anesthesia-alters-membranes hypothesis. Taking a closer look at the root cells of Arabidopsis plants (the lab rat of the plant world) placed under anesthesia, the scientists observed that diethyl ether and lidocaine both affected how these membranes recycle little bubble-like shipping containers called vesicles. Because many complex membrane components must all be working properly to make vesicle recycling work, the authors suggest that this evidence supports the idea that anesthesia works by screwing with cell membranes.  

Other recent research has offered support for this idea. Intriguingly, one paper even hinted that the action of anesthetics may extend – almost mystically, in my opinion to the electron spin of proteins embedded within membranes. Others have suggested that the anesthesia mechanism may involve changing the thickness of the cell membrane or its mechanical properties, which may then in turn affect protein function.

Anesthesia may even mess with the actions of proteins lashed together into complexes called “lipid rafts” that drift within the phospholipid sea. If so, it could cause membrane proteins and vesicle trafficking to go haywire, which could short circuit action potentials and thus put an organism to sleep.

Perhaps the most convincing evidence for the membrane hypothesis is the most bizarre, and it has been known about for some time: placing humans, animals, and even plants under high pressure reverses anesthesia’s effects. Wait, what? But it is true. Perhaps pressure stabilizes membranes in a way that makes them impervious to anesthesia. 

The high pressure reversal of anesthetics, the incredible fact that all life forms – not just plants and animals -- can be anesthetized, and the alteration to root membrane functioning in plants all suggest that membranes are the true target of anesthetics, the authors conclude.

However, if this is true, this counters mainstream scientific opinion, which prefers the receptor hypothesis. And if receptors are the true target of anesthetics, here too plants share similarities with us. Glutamate and GABA receptors, major regulators of the central nervous systems in animals that have been mentioned as possible targets of anesthetics, are present also in plants.

The debate about whether anesthetics act on membranes or receptors has been fought for a long time. Resolving it has proved difficult because, for a variety of reasons, studying living tissues of animals under anesthesia is hard.

Plants, the authors suggest, may resolve this dilemma, especially since we now know they suffer the same loss of action potentials that we do. Our green, stationary friends may be the perfect subjects to reveal, according to the authors, “the elusive mechanisms underlying both anesthetic and the phenomenon of consciousness.”(italics mine)

No one is saying that plants are conscious. But people. Plants. Consciousness.

Wow.

Reference

Yokawa, K., T. Kagenishi, A. Pavlovič, S. Gall, M. Weiland, S. Mancuso, and F. Baluška. "Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps." Annals of botany (2017).