Why is all this microbiome stuff happening now?

We have been observing microbes since 1676, when Antonie van Leeuwenhoek, a wealthy Dutch draper, perfected a set of tiny spherical lenses that revealed “animalcules”: these animalcules were everywhere. He found them in pond water, and everywhere else he looked, even in his own mouth. His discovery led him to say, “The number of animals in the scurf of a man’s teeth are so many that I believe they exceed the number of men in a kingdom.” Nobody really believed him.

Why then, did it take more than 300 years from 1676 to realize that we have more microbes than human cells?

To be fair, it’s really tough to see what’s going on at the microscopic level in a live specimen even if you’re equipped with a microscope and even the best microscope images are very limited. You’d have to cut a chunk out of your specimen, slice it very thin, and mount it on a piece of glass. Even then, you only get to see a tiny window into what’s going on, and the resolution is not that great because it’s limited by the wavelength of visible light.

Another possibility to detect and observe microbes is to grow them. A sample is taken and placed on a petri dish containing nutrient gel. Then, you see what grows. You’d be surprised—but not everything grows! 99% of microbes can’t grow in the lab. Nutrient gel has good nutrients … why wouldn’t everything grow on it? It turns out that the vast majority of microbes have evolved so specifically, that they cannot live without human cells! They wouldn’t grow on a culture plate.

How did science miss something this big? Microbes are about ten times smaller than human epithelial cells and they’re everywhere, so, unless you know what you’re looking for it’s difficult to see the big picture through a microscope. It was only when scientists could see through the lens of next generation DNA sequencing that it became possible to take a proper roll-call of who was there.

Advances in science now allow us to “see” DNA and we can now study ecosystems that were previously too small to study. The Polymerase Chain Reaction, discovered by Kary Mullis in 1983 allows us to identify microbes by deciphering their DNA. Over the last few years, the cost of sequencing DNA has now fallen enough to make this type of research possible.

It took a massive leap in observational power to shift our perspective. We needed to see the microscopic world at the genetic level so that we could take an inventory of what was there.