What is the smallest unit of life? If a living thing is like the rain, what are the raindrops it is made of?
This question has led thinkers over the centuries to posit the existence of exotic-sounding concepts. Entelechy, monads, infusoria. If you are writing a fantasy novel and need words to describe its magical elements, taking a look at the hypotheses on the substance of life will prove inspiring.
But it is in the honeycomb that humanity found the answer. This tapestry of six-sided wax cells crafted by honeybees is what prompted scientist Robert Hooke to name a plant’s building blocks “cells” in 1665. Under the magnification of his simple but elegant microscope, Hooke saw that plants were made of cells. Soon, we would learn that all living things were made of cells. But what exactly is a cell?
Life as a house
When they were discovered, cells were thought to be hollow. They were seen as conduits for the passage of life juices, much like the holes in a pasta strainer. Cells were bricks that, through the intervention of some external force, added up to a living organism, but they were not in and of themselves alive.
Some disagreed. They thought that cells were alive, and when they organized themselves in the shape of a human body, for example, that body was alive because its cells were alive. Cells as bricks versus cells as tiny living things. That was the debate. Science would end up judging in favour of the latter.
It’s important to cast ourselves back to the 1600s and understand that what Hooke saw through a very rudimentary microscope were walls. Very thick walls. Plant cells, you may remember from elementary school, have sturdy walls, like fences around homes. These walls are made of cellulose, hemicelluloses, and pectin, a gelling agent used in jellies and jams. These walls were easy to see under the microscope. Animal cells, like ours, don’t have walls. They have selectively permeable membranes. Thus, they were thought to be very different (which turned out not to be the case). What they did have in common was this jelly inside of them. If the cell wall is the fence, the jelly is the lawn. What was it doing there? And what did it contain? Light microscopes could not provide an answer.
In 1833, Robert Brown discovered the nucleus of the cell (basically, the house in our analogy). Hence, some cells had walls, others didn’t, but they all had jelly and they had a nucleus. This nucleus became very important to figure out how cells lived and died. We knew that new cells had to arise: after all, if we roll back the clock on the human body, it begins with one cell, the egg, being fertilized by another cell, the sperm. They fuse into one, the zygote, and eventually we end up with an adult human being made up of trillions of cells. How did all of these cells come about?
An illustration of cells with their nucleus in dark red (from Servier Medical Art)]
One of the fathers of cell theory, Theodor Schwann, thought he could see new cells forming around a nucleus, like crystals do. It has since been argued that Schwann, along with the other father of cell theory, Matthias Schleiden, fell prey to motivated reasoning: they wanted to see something under the microscope, so they made themselves see it.
This hypothesis that cells crystallize around a nucleus and grow out from it, like snowflakes, was opposed by others. We now know that this idea is indeed false. New cells arise from older cells. The DNA inside the nucleus is duplicated and the cell splits into two. All cells come from a cell, and new life comes from old life.
But at this point, observing cells under the microscope was like looking at a house using the bird’s eye view of Google Maps. What’s that in the yard? Can’t really see.
The electron microscope changed all of that.
“The cell, too, has a geography”
A light microscope uses light to illuminate a tiny object. An electron microscope, which was invented in the 1930s, uses a beam of electrons instead of light. Electrons are the negatively charged particles that surround the nucleus of an atom, somewhat like planets around the sun. The images we get from electron microscopy are generated based on how the atoms in the studied object scatter the electrons beamed in from the microscope. This allows researchers to see an incredible amount of detail, like these butterfly eggs which look like blimps made of carefully crafted paper.
Scanning electron micrograph of the eggs of a European cabbage butterfly (© David Gregory & Debbie Marshall, Wellcome Images/Wellcome Library, London (CC BY 4.0))]
By this point, the large components of the cell were known to scientists, but electron microscopy allowed them to see them in sharper details and to notice smaller bits and pieces of the cell, so-called organelles (meaning “small organs”). They saw the mitochondrion, the energy factory of the cell, and its double membrane. They saw the endoplasmic reticulum, a network of membranes and sacs that help newly built proteins find their optimal shape. The electron microscope also helped scientists put to rest an old theory: that cells, specifically those of the nervous system, were actually one large continuous network, that there was no such thing as individual neurons. By visualizing the empty space between neurons, through which neurotransmitters get exchanged, it became abundantly clear that our nervous system was made up of discrete cells.
A stomach wall cell, with its nucleus in navy blue and organelles in different colours (from Servier Medical Art)]
Every scientific finding ends up raising more questions and exposing the complexities of the universe around us. The cell is no exception. It is a vibrant, dynamic, elaborate ecosystem, and its understanding was helped by a series of analogies.
When scientists discovered enzymes, i.e. proteins that regulate the rate of chemical reactions without being altered by them, cells were imagined as big bags of enzymes.
Then cells were thought of as chemical laboratories or assembly lines, with the right tools organized in close proximity. We realized that enzymes were not always freely floating about in the cell, waiting to encounter the right substrate by chance. Many were attached to membranes. Others were found inside of compartments within the cells, like toolsheds in someone’s backyard, compartments that would be characterized using electron microscopy and better biological tissue preparation techniques in the lab.
The cell, then, as Nobel-Prize-winning biochemist Frederick Gowland Hopkins put it, had a geography. It wasn’t just a bag.
With the discovery of hormones and vitamins in the early 1900s, and an ever-growing understanding of biochemistry, the cell became thought of as a machine capable of transforming chemical energy.
Now, the cell has taken on aspects of electronic circuitry. It has molecular switches. Its signaling pathways, with one molecule activating another which activates a third, are complex, dynamic networks, often represented the way that an electrical system is laid out on a wiring diagram. As cell scientists moved from being individual anatomists of the microscopic world to becoming members of large, collaborative teams, their idea of what the cell was and what it did shifted accordingly, revealing to them its layers of complexity and collaboration. Being able to see cells live with video cameras broke us free from static images. The use of fluorescence allowed us to track transport within the cell. Cytology, the study of the cell, became insufficient and it was suffused with knowledge gained from genetics, biochemistry, and molecular biology.
The cell is much more than a house and its yard. It is a veritable city.
Bringing cell biology to life
Words can only paint this enthralling ecosystem in the broadest of brushes. Over fifteen years ago, Harvard University’s Department of Molecular and Cellular Biology commissioned the medical animation studio XVIVO to use computer graphics to show the world what this cellular city would look like if we could miniaturize ourselves to enter it.
The result was the award-winning cinematic animation “The Inner Life of the Cell,” which premiered in 2006.
Excerpt from “The Inner Life of the Cell.”
We see red and white blood cells being carried along inside a blood vessel. We see the pockmarked surface of a white blood cell rolling along the inner surface of the vessel, the cell’s proteins interacting with the vessel’s proteins like sticky hairs rubbing against each other. As we zoom closer, we see all manner of proteins looking like coloured clouds and spindly rods.
Inside the white blood cell, we witness the grid of the cytoskeleton, the cell’s scaffolding, growing and being dismantled as needed. We see the walking protein dynein, looking like an alien, strolling on the cytoskeleton with its clown shoes, dragging this massive cargo around.
We see molecules locking arms. We see freight being shipped around. We see DNA being transcribed into RNA, which gets translated into the many proteins our bodies need.
This is life.
When, in the titular 1931 movie, Dr. Frankenstein screams “It’s aliiiive!” he is talking about his patched-up creature. He could also have been referring to the trillions of cells of which his creature was made up.
Take-home message:
- Cells are the fundamental structural units of living things and they were named in 1665 because, under the microscope, they looked like the cells of a honeycomb
- Electron microscopy allowed scientists to see the cell better and to identify “small organs” inside of them named organelles
