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Authors: Adam Rutherford

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Even without a consistent model for reproduction, the innards of cells continued to be explored. In 1831, Robert Brown studied orchid cells.
5
Within them he observed “a single circular areola, generally somewhat more opaque than the membrane of the cell.” He called it the nucleus, the name it still bears today, and we now know it as the central office for the genetic code in all complex organisms.
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As with Dumortier's observation of cell division, Brown's assumption was that the nucleus was not universal. Many thought division was an exceptional means of cell birth, and no such observation of fission had been seen in animal tissue. Plant cells are frequently considerably larger than their animal counterparts, and so the study of flesh trailed the examination of leaves. The nucleus had been observed in some animal tissues, particularly brain cells, but again, was not assumed to be present in all cells. Compounding the issue, the most common type of cell in humans, red blood cells, does not contain a nucleus: it is shed during their development.

The names most closely associated with cell theory in almost every textbook are Schwann and Schleiden. The story Theodor Schwann told was that there was a eureka moment at the birth of cell theory. Schwann and Matthias Schleiden met by chance at a dinner in 1837. Schwann was an anatomist, short and nerdy; sometimes he would not leave his home for days at a time while he examined bodily tissue. Schleiden was a troubled, sometimes suicidal botanist who had been influenced by Robert Brown's identification of the nucleus. Botany and animal biology were separate fields, far from the unification that evolution and genetics would ultimately supply. Over dinner they discussed their work on animal and plant tissue, respectively. The conversation must have become even more thrilling for the other guests as their discussion progressed to the nucleus, that smaller body in the middle of cells. Schwann and Schleiden both realized that the nucleus was the same in plant and animal cells. They rushed without delay to Schwann's laboratory to compare notes. From this point on, the idea that all living tissue was made of cells took hold.

Dynamic though this legend is, Schwann and Schleiden were in fact only partial contributors in the development of a model of life based on cells, and significantly wrong about one major part. Much of the work demonstrating the nucleus in plants and animals had come before them, and the universality of cells had been suggested by others before 1837. It was probably Schwann who first used the phrase “cell theory,” but where he and Schleiden were most significantly off the mark concerned the origin of new cells. Both described the formation of new cells starting with the spontaneous appearance of a naked nucleus in the spaces between existing cells. According to them, that nucleus acted as a seed from which the new cell would emerge, like a growing crystal. It's not as far-fetched as heavenly lemmings, but otherwise it was still reminiscent of spontaneous generation.

Our understanding of the origin of new cells can be largely attributed to Robert Remak—a lost hero of biology, and a victim of politics and race. Remak was a Polish Jew who spent his adult life in Berlin. To get the university position he wanted and deserved, he would have had to betray his Orthodox Jewish roots and be baptized, something he never did. Through his undeniably good science he was eventually given a post of lecturer, followed by assistant professor at the University of Berlin, but this post came with neither salary nor lab. Compare Remak's trajectory with that of his contemporary cell biologist Rudolf Virchow. Born into a well-to-do Prussian family, Virchow was flamboyant and bombastic. Ultimately, he would be described as “the pope of medicine” and “the sole instance of a full-fledged physician-scientist-statesman in our time.” He was six years Remak's junior, but they were appointed to the University of Berlin at the same time.

After careful observation, Remak rejected spontaneous generation in all forms, including that which Schwann and Schleiden were describing. For a decade, he studied all manner of animal matter, including muscle and red blood cells as they grew in frog and chicken embryos; he only saw cells splitting, with one pinching in the middle like a belt on a balloon until it became two.

Virchow followed Remak's work, and year by year edged closer to his way of thinking—that cells were only formed by cell division. In 1854, Virchow declared that “there was no life but through direct succession,” and a year later translated this into a Latin motto:
Omnis cellula e cellula
(“All cells from cells”). He was popular and prominent, and expounded this idea wherever he could, like in his international best-selling textbook
Die Cellularpathologie
. But there was no mention of Remak in any of these writings. Virchow had done little of the work, but had adopted his colleague's toil without giving him any credit. Remak was livid and wrote to Virchow about the Latin summary:

[It] appears as your own without any mention of my name. That you make yourself ridiculous thereby in the eyes of the knowledgeable, since you have no evident embryological expertise, neither I nor anyone else can undo. If, however, you wish to avoid a public discussion of the matter, I would ask you to immediately acknowledge my contribution.

We sometimes forget that science is undertaken by people, with all their personalities in tow. The scientific method is designed to equilibrate for all those idiosyncrasies and usually succeeds. But giving credit where credit is due remains a perpetual problem.
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Nevertheless, Remak, and Virchow for all his sins, had nailed it. Life is cells, and cells only come from other cells. But like a zombie, spontaneous generation still shambled along, lurching up yet again in France in 1860. The man who finally killed it dead was Louis Pasteur. Not yet famous for the sterilization technique that bears his name, Pasteur was ambitious, young, and had twice been denied membership in the French Academy of Sciences.

An experiment by a prominent proponent of spontaneous generation had reignited belief in its existence. Félix-Archimède Pouchet wanted to show that mold would spring forth from hay, even if the hay, the air, and the water used were sterile. Pouchet boiled the ingredients and then cooled them down with liquid mercury. As if by magic, mold appeared on the hay. The Academy wished to sort this out once and for all, and offered up a prize of 2,500 francs to the first person to resolve the theory of spontaneous generation.

Pasteur spotted the flaw: the mercury had a layer of dust on its surface, which was bringing in the mold. So he designed the simplest experiment imaginable. His version of Pouchet's setup was to have two flasks containing a sterile but rich broth, one that would soon go cloudy if exposed to microbial life. One flask was left open while the other had an S-shaped curved neck protruding to one side. Pasteur figured that microbes carried on airborne dust particles would reach the broth in the first flask, but that the swan neck would not allow these contaminants into the broth in the second flask.

Within days the open flask was cloudy. But the swan-necked flask was perfectly clear, and remained so indefinitely. As a control, Pasteur snapped off the swan neck and observed the broth growing cloudy over the next few days. Pasteur claimed the cash and was duly elected to France's scientific elite.
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The ultimate fate of this incorrect yet persistent theory is best described in Pasteur's own words, spoken at a lecture in Paris in 1864: “Never again will the doctrine of Spontaneous Generation recover from the mortal blow struck by this simple experiment [. . .] those who think otherwise have been deluded by their poorly conducted experiments, full of errors they neither knew how to perceive, nor how to avoid.”

These are harsh words, but true. Thousands of years of biological superstition were swept away by an essential feature of science: the experiment. And with that swan-necked flask, cell theory was completed. Like all great theories, it's a fusion of ideas, based on observation and affirmed by experimentation. It is also one of the great nodes of biology. The work of dozens of men and hundreds of years of investigation into the stuff that life is made of can be summarized in two sentences:

  1. All life is made of cells.
  2. Cells only arise by the division of other cells.

The implications of this idea are profound, as grand theories should be. It covers all life, a simple but comprehensive description of the innumerable inhabitants of the living earth. But, as we already know, there are trillions of different types of cells. In the case of red blood cells, for example, those found in humans are different enough even from those of our nearest primate cousins that they cannot be exchanged without serious consequences. By the time we start looking at species as distant from us as chickens, we find, as Remak did, that their red blood cells do contain a nucleus, unlike our own. The first component of this grand idea shows that the diversity of life on Earth is embedded in the magnificent range of cells. The second shows how that diversity came to be in the first place.

Change over Time

At about the same time that Schwann, Schleiden, Remak, and others were observing how cells behave, across the English Channel a youngish family man was busy reflecting on his overextended gap year. Charles Darwin was slowly and meticulously putting together an overwhelmingly compelling case that described how creatures evolve. Evolution, the idea that species are not immutable, was already being contemplated as a concept in the nineteenth century. But the process by which they change was unknown. Darwin had spent five years traveling thousands of miles on HMS
Beagle
, collecting specimens from the far side of the world. Upon returning he married his cousin Emma Wedgwood; they were both grandchildren of the pottery magnate Josiah Wedgwood. They settled in Down House in Kent, and, untroubled by financial pressures, Darwin began chiseling out a splendid idea. In 1859, after years of scientific and personal struggle, he published
On the Origin of Species
.
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In it he sets out the second grand unifying theory of biology, one describing the process by which evolution takes place.
10

Unlike the microscopists in Europe, Darwin was primarily concerned with whole animals—the macroscopic world. He observed when comparing individuals in any population that there is a natural range for any given physical characteristic. This variation is the means by which those individuals can have a competitive advantage over others. In an imaginary population of anteaters, one with a slightly longer tongue than his contemporaries may be able to root out more juicy termites and may be better fed and healthier as a result. This could have the effect of making him live longer or maybe making him a more attractive mate to a female anteater. Consequently, this anteater may have more baby anteaters, each potentially carrying that longer tongue. After a few generations of that success, because that tongue is a useful thing, long-tongued anteaters may come to dominate the population and become the norm. Over successive generations the species will change. In contrast to earlier theories, Darwin observed that it was not characteristics acquired during a being's lifetime that were passed on to offspring. Years of obsessive measurements led him to establish the principle that for each and every trait—an anteater's tongue, hair color, and so on—it was the variation of that characteristic across the population that conferred advantage for an individual. Those traits would become more common in a population because the advantage they conferred would play out as greater reproductive success.

There are other significant selective forces, such as the complexities of sex, where males puff themselves up to win a female, or females exercise seemingly whimsical choice over males. But natural selection is the overarching force that has shaped the living world in which we live. It's a system of trial, error, and revision. Evolution is blind and has no direction. Species are not more or less evolved, nor are they higher or lower, as they were once and sometimes still are described. Through iteration, they are merely better adapted to survive in their environments. In an experiment that really should not take place, an orangutan wouldn't last two minutes in the boiling submarine waters of a hydrothermal vent, despite being sophisticated enough to use tools in the jungles of Borneo. Down in the hot sea of a vent, though, hundreds of species, including the six and a half foot long giant tubeworm and dozens of species of bacteria, are quite content to eke out their existence. Change is the norm, and adaptation is success.

In the 150 years since the
Origin of Species
was published, millions of scientists have poked and pulled at the theory of evolution; unpicked, tweaked, and yanked at it in every conceivable way. They have observed countless species from aardvarks (or anteaters) to zebras to study their behavior. They have created simulations of myriad populations first with mathematical models, later with computers, and have pushed and pressurized their artificial environments to see how they adapt over successive generations. They have bred and crossbred inestimable species to observe how inheritance works, to see where advantage lies in the next generation. They have let tanks of bacteria reproduce for decades and witnessed descent with modification in action. In the modern era, we have deciphered a host of genetic codes and seen exactly the differences in DNA that reflect one species becoming two, each finding a niche into which they are better suited. We've seen populations of bacteria adapt to the hostile action of antibiotics and, distressingly, emerge resistant. While the initial model that Darwin laid out has been modified and fleshed out, the “one big argument,” as he described it, has survived intact throughout the necessary battering that an idea of this magnitude demands. This is why it is called the theory of evolution by natural selection. The colloquial meaning of the term
theory
as a hunch, or guess, or plain old stab in the dark, is woefully puny next to its scientific meaning. When scientists talk about a theory they are aiming at the top of the pile of ideas: a set of testable concepts that all point to and predict a description of reality that is so robust it is indistinguishable from fact.

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