CGMs, Honeybees, Neutrophils, and Bombardier Beetles: A Surprising Connection

I’ve written a couple of articles recently (here and here) about CGMs (continuous glucose monitors). While researching the components of the sensor technology, I came across an incredibly cool series of connections that I wanted to share.

You all know that I consider “analogy as the core of cognition” (I am shamelessly stealing this phrase from Douglas Hofstadter. Watch his lecture of the same title - it is fantastic). As Professor Hofstadter says in the lecture:

I now make an observation that, though banal and obvious, needs to be made explicitly nonetheless — namely, things “out there” (objects, situations, whatever) that are labeled by the same lexical item have something, some core, in common; also, whatever it is that those things “out there” share is shared with the abstract mental structure that lurks behind the label used for them. Getting to the core of things is, after all, what categories are for. In fact, I would go somewhat further and claim that getting to the core of things is what thinking itself is for - thus once again placing high-level perception front and center in the definition of cognition. (emphasis mine)

- Douglas Hofstader

According to the professor, we make sense of the “new & unknown” with the help of the “old & known”.

In that spirit, I want to show you how CGMs, infections in WWI, honeybees, immune system cells, laser cannons, and Bombardier beetles have a lot more in common than you might realize.

Solving Infections in WWI

In the US, it’s easy to think of infections as relatively minor things. Modern healthcare may not be great at dealing with chronic disease, but it has done a hell of a job at addressing acute care situations like traumatic injury, burns, and infections.

But for most of human history, infections have been one of our species’ biggest enemies. In fact, we have papyrus evidence indicating that the topic of infections has been vexing physicians at least since the days of the Egyptians.

The danger of infection is even more pronounced during times of war. Bullet wounds, stab wounds, incendiary burns, and compound fractures are just a few of the injuries that can lead to life-threatening infections on the battlefield.

That is why doctors during WWI drew on a time-honored medicine for dealing with wound care: honey.

Physicians have long known that honey contains antimicrobial properties, and modern science has confirmed those claims. But what gives honey its antimicrobial properties?

It turns out that honeybees produce an enzyme called glucose oxidase during the honey-making process (we’ll come back to this enzyme in a minute). In the presence of oxygen, glucose oxidase converts glucose into two byproducts: gluconolactone and hydrogen peroxide.

Credit: Wikipedia

Hydrogen peroxide is a special molecule, but to understand why it’s so cool, we need to talk about neutrophils and laser cannons.

Neutrophils: Cell-Sized Assassins

Evolution has equipped your body with a host of biological weapons to stop bad guys like bacteria from causing mayhem inside of you. Most of you are familiar with one of the big guns in that fight: the immune system.

Within the immune system, one of our lines of defense is a special group of cells called white blood cells. White blood cells are like the armed forces of the body: when enemies raise their heads, the WBCs spring into action to restore order. And just like the armed forces have various branches (Army, Marines, Air Force, Navy, Space Force, and Coast Guard), so too WBCs come in different forms depending on the function needed.

The branch that connects to our story is a group called the neutrophils. Neutrophils are like the Marines - they are the first ones on the scene when trouble (infection or tissue injury) occurs.

Let’s say you get a wound and a nasty bacterium makes its way into your body. Immediately, a signal gets sent for the neutrophils, and they come storming in hot & heavy. Upon spotting the enemy, they engulf the bacterium (a process called phagocytosis) and proceed to fry it to death with a laser cannon.

Guess what type of laser cannon they use to roast the bacteria? You got it: hydrogen peroxide.

Credit: Ward Round Stuff

Neutrophils use hydrogen peroxide as part of the myeloperoxidase-hydrogen peroxide-chloride system to essentially burn their victims to death.

Biology is so cool.

But it gets even cooler.

Bombardier Beetles: Masters of Explosives

When evolution stumbles across an elegant solution to a problem, it often gets re-used in new and interesting ways.

Perhaps one of the more fascinating examples of hydrogen peroxide’s use as a catalytic agent is in the Bombardier beetle:

Credit: Matt’s Bombardier Beetles (no relation to yours truly)

But a picture really doesn’t do this little guy justice - watch this :20 second video to see its explosive rear-end in action:

The Bombardier beetle combines hydrogen peroxide with another chemical called hydroquinone, stews it with a couple of enzymes (catalase and peroxidase), and proceeds to eject 212-degree caustic liquid 500-1000 times per second at would-be predators.

Come on…that’s awesome!

Tying It Back To CGMs

When we were talking about honey, I told you that we would re-visit an enzyme called glucose oxidase. As we discussed, glucose oxidase is special because it converts glucose into several byproducts, one of which is hydrogen peroxide.

We saw how hydrogen peroxide has lots of interesting uses in nature:

• It imbues honey with antimicrobial properties

• It equips neutrophils with a weapon to destroy invading bacteria

• And it gets packaged up by Bombardier beetles to help defend itself

But we can also use this knowledge to reverse-engineer the amount of glucose in a system. By combining glucose oxidase with an electrode, you have the foundation of the sensor technology used in a CGM like the Dexcom G6:

Credit: Shridhara Alva, PhD. Abbott Diabetes Care

With a few modifications, you can even create a wired enzyme-based set up that bypasses the need for tracking hydrogen peroxide, such as the type used by Abbott’s Freestyle Libre 2:

Credit: Shridhara Alva, PhD. Abbott Diabetes Care

This is why I find biochemistry such a fascinating field. Biochem isn’t just about memorizing endless metabolic pathways. Rather, it’s the study of the marvelous interconnections that exist in the world around us. Whether we are examining honeybees or immune system cells or beetles, the rich connections of the natural world are constantly showing up in new and exciting ways.

The next time you look at your CGM, think about how cool it is that a random enzyme found in honeybees

¹

is helping scientists to track your glucose levels. Science can be pretty awesome!

1. Don’t worry, no honeybees are harmed in the making of CGMs. Glucose oxidase is also produced by fungi to ward off bacterial predators, which is how scientists first discovered the enzyme.