Many great advances in cell biology followed improvements in their tools; in 1665, Robert Hooke first discovered cells with the help of the compound microscope he developed himself (diagrammed by him above).

It’s easy to take for granted the amazing scientific discoveries of the last few centuries, or even just the last decade, which were once incredible breakthroughs. One of the most fundamental discoveries for modern biology was the discovery of the cell. From the largest cells—nerve cells as long as 39 feet in giant squids, and the single-celled ostrich egg weighing in at three pounds—to the smallest bacterial cells, all cells share common characteristics and are the basic building blocks of all life as we know it.

So how did we learn that life is made of cells? Like many scientific discoveries, the first cell observation was not simply due to a few people being more perceptive than their predecessors; it was enabled by many factors, technological and social, falling into place.

Truly, the invention of the microscope, combined with the efforts of many very observant biologists, seeded the field of cell biology. Although obscure, the origins of the microscope most likely lay with the hands of several Dutch lens-grinders in the early 1600s. Scientists throughout Europe quickly snatched up this amazing new tool and carefully recorded and shared their many observations of the world around them that had previously been inaccessible. The first microscopes were basically a viewing tube with one lens, like a magnifying glass, placed inside. As with microscopes today, an observer would place their eye on the top and their sample underneath the tube. The first microscopes developed could probably only magnify a sample’s image tenfold.

Many European researchers took these new microscopes and looked at tissues and other biological samples, some making their own improvements to the microscope. Robert Hooke, experiments curator at the Royal Society of London, is generally acknowledged as being the first to observe cells. In about 1660, he improved the existing single-lens microscope design by placing a second lens in the viewing tube. When appropriately placed relative to the other components, the second lens allowed for much greater magnification of a sample; he created the first compound microscope. Modern compound microscopes can magnify a specimen 1000 to 2000 times.

Using his newly developed microscope, Hooke made many detailed drawings of all sorts of biological objects around him, from insect parts to fungus to feathers, and much more. In 1665, he published his drawings in his book Micrographia. His most celebrated drawing from Micrographia is a thin section of cork, made from oak trees. In the thin slice Hooke observed, he found it to be “porous, much like a honey-comb.” He named the tightly-packed cavities “cells,” after the Latin word “cella,” meaning “a small room.”

Around the same time as Hooke, in the Netherlands, Anton van Leeuwenheok was also busy improving upon the original microscope designs, which led him to be the first to observe living cells. Van Leeuwenhoek was a cloth merchant, and to count threads he used magnifying lenses that magnified the cloth approximately threefold. He developed new ways to polish and grind the lenses; he increased the existing single-lens microscope’s magnification to 270-fold magnification. With his improved microscope, in 1673 he was the first to see living organisms in pond water. While he called them “animalcules,” they’re now known to us as microorganisms.

Several other researchers during the 1600s were also looking at various biological specimens under microscopes, and this great demand soon made it quite apparent that even better microscopes were needed. Even with improvements, many imperfections in the microscopes could produce misleading observations; it was often difficult to know whether researchers saw actual cells, or just the result of aberrations, causing something to look like cells. Recognizing the need, lens makers throughout the 1700s worked to reduce aberrations; at the beginning of the 1800s, their efforts finally paid off with the creation of “achromatic lenses.” However, these lenses still had problems and, throughout the century, they were improved upon to create “apochromatic lenses,” which have even fewer aberrations.

As views of what was going on in these cells improved, scientists developed many theories for how the cells functioned and consequently got into many heated debates. One of the first was over the function of the cell nucleus. We know now that the nucleus is where the cell keeps its DNA, and that the DNA makes up the genetic blueprint for the cell (and for the organism as a whole). Discovered in 1833 by Robert Brown, it’s not too surprising that the nucleus was the first organelle (specialized cell component) found; it is a large, round cell part, often near the cell’s center, and, importantly, it is relatively opaque, making it visible even with poor microscopes.

Mattias Schleiden, a German botanist and microscopy master, long examined plant cells under the microscope. Because plant cells have very rigid cell walls, they appear very different than animal cells, which lack walls and vary greatly in appearance from tissue to tissue. Consequently, Schleiden thought for a long time that plants were made of cells but animals were not. However, because Schleiden also came to believe that the nucleus was the most important and defining cell part, when his associate, the German zoologist Theodor Schwann, found similarities between plant and animal cells, such as the presence of a nucleus, he came to accept that all living things were made of cells. In 1837, this led to Schwann’s being the first to conclude that cells were “basic units of life.”

While others generally accepted that cells were life’s basic building blocks, the debate turned to how these cells were created. Schleiden believed that the nucleus generated a new cell around it in layers in a purely mechanical manner, much the way a crystal forms from around a small seed crystal (or, confusingly, “nucleus”). However, others were already describing cell division, the process by which the nucleus and surrounding cell duplicate their material then split into two cells; their observations went against Schleiden’s nucleus theory.

Once again, the scientific debate was resolved by the availability of improved tools. In the decades after 1850, methods of preparing samples for microscope viewing were developed, aided by the increasing availability of dyes that colored only specific parts of the cell. Carmine red, the first stain, had been used for centuries as a dye in Mexico, where it was made by crushing chochineal insects. Carmine red selectively stains the nucleus, making it much clearer to see microscopically than before. Such advances undoubtedly contributed to Rudolf Virchow, a Germany physician, settling the cell origin debate in 1855: He reported, based on his observations, that all cells come from the division of other existing cells, not just from a cell nucleus.

Schleiden, Schwann, and Virchow developed the three fundamental parts of the cell theory which is still taught today: (1) All living things are made up of one or more cells. (2) Cells are the basic units of biological structure and function. (3) Cells can only come from preexisting cells.

Armed with this basic knowledge of cell biology, further investigations into the intimate, complex workings of cells were later made possible with the use of more advanced microscope techniques, specific dyes, and other tools that developed, such as ultracentrifugation. These tools allow scientists to make new discoveries to this day. For example, the University of California, Santa Barbara, has many powerful microscopes, including electron microscopes that can magnify the image of a sample to around 500,000-fold (allowing resolution of individual proteins and DNA molecules). Such tools allowed researchers to greatly increase their understanding of the many different cellular components, or organelles, throughout the 20th century. These organelles, and their stories, will be discussed in Part II.

For more on the early history of cell biology, see William Bechtel’s Discovering Cell Mechanisms: The Creation of Modern Cell Biology, Arthur Hughes’ A History of Cytology, Henry Harris’ The Birth of the Cell, Wikipedia’s “Cell Biology,” and Wikipedia’s “Microscope.”

Biology Bytes author Teisha Rowland is a science writer, blogger at All Things Stem Cell, and graduate student in molecular, cellular, and developmental biology at UCSB, where she studies stem cells. Send any ideas for future columns to her at


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