From Jones and Bartlett, a book on Stem Cells from Dr. Ann A. Kiessling and Scott C. Anderson:

Selected Articles:

May 7, 2003

Aristotle's Chickens

Aristotle came close to discovering stem cells more than two thousand years ago. Will we have to wait another two millennia for a therapy?

By Scott C. Anderson

Aristotle strode slowly in the shade of the covered walkway, gesturing as he spoke. In his wake was an excited group of young students, straining to hear his every word.

"Welcome to the Lyceum!" he shouted, spreading his arms expansively at the surrounding campus. The students looked around, taking in the olive trees, flower beds and various handsome buildings. A gurgling irrigation ditch wound its way through the serpentine gardens, keeping it lush year-round. Over the years many philosophers had found their way to this idyllic grove; it was easy to see the attraction.

Plato and Aristotle"This academy is unlike the others in Athens," he declared. "Those schools spoon-feed their pupils a simplified world, populated with imaginary, perfect forms. It is candy for the brain -- and just as nourishing! The Lyceum, on the other hand, is grounded in the real world, grubs and all. Your course of study here will be much more rigorous. So, if you wish to join those frivolous philosopher kings and lodge your head in the clouds, now is your chance to leave."

Aristotle waited, whistling quietly and tapping his foot, but no one left. "Okay, then, you've been warned. At the Lyceum, you will get your hands dirty!" The students traded slightly worried looks, but Aristotle didn't give them time to dwell on this pronouncement. He continued walking, making his way toward a familiar-looking building.

"This is our barn. The more pampered among you have likely never set foot in one of these buildings. Here we have kept and bred thousands of animals." As the smell of urine and manure hit them, the students grimaced in unison.

Seeing their reaction, Aristotle said, "Here you may close your nose, but you must keep your eyes and your mind open!

"The greatest thinkers of our time know much about the heavens, but precious little of our day-to-day world. When it comes to flesh and blood, the lowliest farmer puts them all to shame. A philosopher can make a decent living propagating noble lies, but a farmer can starve to death merely by straying slightly from nature's true path."

"But professor, are you mocking your own master, Plato?" said a student, timidly.

"Ah, shrewd of you to notice. Well, young man, Plato is very dear to me. And the truth is dear to me. But really, the truth is dearer than Plato!"

Too much for PlatoInside the barn, Aristotle gently moved aside a clucking hen, snatched an egg from the nest, and held it up for the class to see. "This simple white shape is beyond the ken of these so-called geniuses!" A few of the students shared nervous glances. The rumors were true, they realized: Aristotle flouted authority, and not timidly, either.

"How does a chicken come from this egg? Is it not a marvel? And yet, in my travels, I've found a suffocating ignorance about chickens, eggs or animals in general." A look of anger and frustration crossed his face. "But I have seen wondrous things in these eggs -- and believe me, these wonders will change the way you look at life!" Aristotle became more animated as he warmed to his favorite subject.

"At the Lyceum, we have studied eggs for many years, and your class will carry on the tradition." Moving to a nearby table, he pointed at the rows of cracked eggs on display. "Here you see how we study the growth of a baby chicken. This science is called embryology, and it provides a remarkable insight into how life begins."

"Theo," he said, pointing to one of the older students near the back of the crowd, "show us what you're studying here."

"Yes, professor," said Theo, making his way through the younger students, who respectfully cleared a path for him. "As instructed, I have set out twenty eggs on the table. The first one was laid today and the next one was laid yesterday and so on. As you move down the table, each egg is a day older than the previous one. Thus, you can see twenty daily stages in the growth of the chicken embryo."

"So, Theo, what have you discovered? Is there a tiny chicken in the eggs that simply swells to fill the egg, as some revered professors would have it?"

"Oh, no," said Theo, "You're thinking of preformation - the idea that an animal simply uncurls like a flower bud - but it's much more interesting than that. Look at the second egg on the bench, the one that's a day old. It has nothing that looks like a chicken in it at all. But then look here." Theo pointed to the third egg on the table. "You must each come forward and look closely. You will see a small red spot." The students approached the table one by one and bent over the egg. When they saw that the red spot was pulsating, they reacted with varying mixtures of surprise and disgust.

"What do you think the red spot is?" asked Aristotle.

"Well, professor, if you follow it through to the older eggs, you can see it becomes a primitive heart, and after only two days it's already beating."

"But how can that be?" asked the professor. "There are no other visible organs yet! Where is the rest of the chicken?"

"Apparently, this is how the chicken starts -- with certain organs sprouting first, and the rest filling in later," said Theo, with a satisfied look on his face.

"It reminds me of how an artist creates a painting. First a sketch is created, then the parts are filled in, one color at a time," said Aristotle.

"Perhaps," said Theo, cocking an eyebrow, clearly not convinced.

Aristotle smiled. "Okay, if you don't like that metaphor, try this one: The white of the egg is like milk. As you know, when you add rennet to milk, it curdles and forms cheese. Could that be how a chick develops?"

"In the case of a chicken, I suppose that the semen of the rooster would be analogous to the rennet?" asked Theo.

"Precisely. Rooster semen is how the egg gets fertilized, of course. Fertilization triggers a series of actions, like a pebble starting a landslide. After a while the organs begin to sort themselves out like cheese curds, hardening along the way," said the master.

"Well, something of the sort certainly seems to be the case," said Theo. "The egg goes from simple white and yolk to something quite complicated. It seems to form itself out of nothing. It's quite remarkable!"

"And when does the development stop?" asked Aristotle.

"The chick continues to develop until just before it hatches. After it hatches, it stops developing and starts to grow, with few subsequent changes in body plan," said Theo.

"Is that a hard and fast rule?" asked Aristotle

"Well, actually, no. We've been able to put out the eyes of freshly-hatched swallows and watch them grow back intact." A few of the students blanched, but Theo seemed not to notice. "So there is some limited ability to regenerate tissue even after hatching. But it doesn't work with older birds."

"So at some point after birth, the animal can no longer regenerate tissue?"

"Actually," replied Theo, "some animals, like lizards, can regenerate body parts even as adults. But it's a limited phenomenon - the lizard can only regenerate its tail, not a leg, for instance. Although, in many animals, certain organs like the liver can regenerate. This, we suspect, is the source of the Prometheus myth." Theo turned to face the students. "As you all know, Prometheus stole fire from the gods and was condemned to have his liver pecked out each day by an eagle. Every night his liver regenerated, only to provide a continuous feast for the bird and endless torture for the hapless Prometheus."

"You know," said Aristotle, "many people think the story of Prometheus is really about philosophers being punished for revealing the secrets of jealous gods. What do you think, Theo?"

"Well," said Theo, swallowing hard, "I certainly hope not. We're always trying to expose the secrets of nature, but so far the gods have been smiling on us."

"Professor?" A hand shot up from the crowd.

"Good, a question! Speak!"

"Well, professor, my father sent me here to become a doctor. How can chicken eggs and lizard tails possibly help me with that?" asked the student.

"A good question!" Aristotle said. "Theo, do you have a good answer?"

Theo looked thoughtful. "Professor, we have looked at eggs from over five hundred animals, and they all follow a similar pattern. We think, as incredible as it sounds, that even humans develop like these chickens."

The students looked startled. They started talking among themselves, and several came back over to the table to look at the eggs again.

"That's impossible!" said one. "Humans don't lay eggs!"

"No - at least not that we can see," agreed Aristotle. "Admittedly, it's difficult to believe. And yet, the evidence is not debatable. Every animal we've looked at goes through the same basic development. There are differences, to be sure, but the beginning stages of each animal are remarkably similar. Astonishingly, a chicken embryo looks much like an early human embryo." Aristotle paused to let the idea sink in. For many, this was a disturbing chain of thought, and they tried vainly to conceal their discomfort.

"Later in development the animal starts to show deviations from this familiar prototype. Only then does it start to declare its own unique heritage and assert those special qualities that make it a horse, a fish, a chicken... or even a human being," said Aristotle.

"But professor, if humans are so much like other animals, why can't we regrow limbs or eyes like they can?" asked another student.

"That's an excellent question! How does development get turned on again for some animals and some organs, but not others? As we learn more about development and regeneration, we may someday be able to grow new arms if one is cut off, or to restore sight for the blind. What we've seen here makes us think that some of these miracles might be at hand.

"But don't take my word for it! That is not how we do things at the Lyceum -- you will see this with your own eyes over the coming months. Observe, and you will learn. Perhaps you will change the world!"

Over the next few years, Aristotle's students would continue to study subjects that other scholars considered base and disgusting. It was clearly beneath the dignity of an aristocrat to dissect an animal or to talk to a fisherman about the life cycles of fish. Aristotle scandalized his sponsors by inviting farmers to teach husbandry. The idea of Athen's finest being tutored in barns by uncouth commoners was galling.

It was a major departure from the teachings of his old master, Plato, who found solace in a mental landscape of mathematically perfect forms, unburdened by the messy fecundity of real life. Plato felt that only philosopher kings could see through the distracting imperfections of reality to the true form and purpose of life. Obviously, such refined thoughts could not be expected to flower in the mind of the common man, so Plato conceived of the noble lie: a simplified mythology designed to bind the citizenry together.

Plato's called his noble lie the "myth of metals." In the form of a Socratic dialog (Plato often shamelessly enlisted his dead master Socrates to make philosophical points) he posited that people come in three different classes, each with a different metal coursing through their veins. Rising up the social ladder, there is iron in the blood of the laborer, silver in the blood of a warrior and, of course, gold in the blood of philosopher kings. Thus ordained, each person should therefore perform the work to which he or she was born with a minimum of fuss and protest. Also implicit in this myth is that the classes shouldn't intermarry, lest they improperly amalgamate their metals. This myth is surprisingly similar to the Hindu caste system that still divides people into exclusive classes.

In contrast to Aristotle's free-wheeling democracy, Plato's noble lie creates a hierarchy where people are not born equal and have limited room to move. He knew it was a lie, but he hoped that its acceptance would lead to a better society - one with fewer blemishes and much closer to his ideal world.

The noble lie has proven to be quite popular with rulers and despots of all stripes, who relish its ability to rally a credulous citizenry around a common cause. The only problem is that it is - after all - a lie. As compelling as it might be within a given culture, it is arbitrary and can easily fall victim to another culture with a better lie - or worse yet, one operating under no false pretenses at all. At the end of the day, the truth will trump a lie every time. But in the short term, a good mythology, like Hitler's Aryan master race or the promise of a noble afterlife replete with heavenly virgins, can do wonders to inspire the troops. As these examples show, even after two thousand years, the noble lie still gets a lot of traction.

Noble lies aren't the exclusive domain of tyrants and kings; they are often created by popular artists. Mary Shelly crafted one of the most trenchant myths of our age: the scientist as Dr. Frankenstein. This brilliantly grotesque icon has been used to demonize virtually every major medical advance since 1818, including blood transfusions, skin grafts, vaccinations, organ transplants and stem cell research. This literary tradition was extended by Aldous Huxley, who gave Dr. Frankenstein a Brave New World to live in. These mythologies are direct descendants of Plato's noble lie, attempting to formulate a more ideal world. The problem is that they are hysterically anti-scientific.

Plato and Aristotle set up a dichotomy between virtue and liberty that is still argued today. Whereas virtue may be protected by the application of a clever mythology, it is always at the expense of liberty - the freedom to challenge the very underpinnings of the virtuous mythology. A good leader will pick nuanced virtues that enhance the cohesion of the citizenry without trampling too many rights. A bad leader will use virtue as a bludgeon to enhance his own circumstances. The standard problem with philosopher kings is that they are not always very thoughtful people, which pretty much sours the whole deal.

But if virtue suffers from problems at the top, liberty is even more frightening to many people - and not just the aristocracy. Science and democracy place ordinary citizens in a position to observe and draw logical conclusions. For poorly educated people, this is a form of torture. So, Plato's noble lie can be seen as self-fulfilling: by entrusting only the philosopher king with thinking, the population is dumbed down to the point that they would prefer someone else to do the thinking for them.

Liberty simply places too many demands on an uneducated citizenry, and that's why Aristotle attempted to make education contagious. While Plato placed truth in the heart of a chosen few philosopher kings, Aristotle found it in the evidence of his own eyes - or anyone else's eyes, for that matter. Aristotle trusted the common man to learn from nature and then spread the word. Apart from their eyes, the only tool they needed was logic, and Aristotle laid out some simple rules for that as well. Aristotle is considered to be the father of formal logic, but in his view there was often more innate logic in the hardscrabble farmer than the insulated nobleman.

The powerful coupling of logic with observation generated unprecedented enhancements in the quality of life. Many of Aristotle's discoveries led directly to better food production and improved health. Along the way, Aristotle was laying the groundwork for the scientific method - where reality has the last word, not the king. It was an idea as potent as it was dangerous.

Aristotle was the first - and arguably one of the best - biologists in history. He and his students witnessed the stage-by-stage embryological growth of hundreds of different animals. They didn't have the instruments to see the fine detail, but by concentrating on the large eggs of fish, amphibians, reptiles and birds, they saw that animals started without a preconceived form and then development followed a familiar sequence that repeated itself reliably throughout the animal kingdom. This was an enormous conceptual break from the prevailing theories of preformation, which posited that animals are fully formed at conception and merely grow in size, not complexity.

Importantly, he and his students understood the tantalizing connection between embryological development and regeneration. They understood that growth was not the same as development, and that developmental processes held the key to rejuvenating tissue. They also noted that when development stopped, it seemed impossible to start it up again. They were right at the cusp of the stem-cell quandary.

Aristotle tackled so many subjects we shouldn't be surprised that he got some of them wrong. His formidable observational skills were often subordinated to his commanding powers of persuasion, and more than one shaky theory benefited greatly from his gift of gab.

Oddly, as great as he was at observational science, Aristotle never really ventured into experimental science. A good experiment goes beyond mere scrutiny to actually interfere with nature, usually breaking something in the process. Based on the failure, you may be able to extrapolate the function of the broken part. The credit for that major breakthrough belongs to Strato, one of Aristotle's successors at the Lyceum. This lack of experimentation led Aristotle to some false conclusions, such as that a heavier object falls faster than a lighter one, and that neither accelerate as they fall.

Both Plato and Aristotle mused about the obvious difference between living and inanimate matter. Plato felt that vital spirits inhabited living creatures, and Aristotle seemed to agree, although he tied spirit more to the degree of motility, with mollusks and urchins on the bottom rung and humans at the top. In that sense, Aristotle was almost verging on a primitive evolutionary theory, but he stopped short, believing that the species were immutable.

As biology has matured, it has become increasingly mechanistic and far less spiritual. Especially with the discovery of DNA and protein synthesis, life is understood more and more as a product of convoluted biochemistry, not a mysterious vital force. Nevertheless, religion has kept its faith in the soul and the spark of life, and even in biology there are those who still hold the torch for vitalism, albeit under the more scientific rubric of holism or ecology. Incredibly, these important concepts were first developed and debated during the lifetime of one man, and the debate continues to occupy us over two millennia later.

Even when he was wrong, there was often a poetic flavor to his conjectural flights. For instance, his likening of embryogenesis to cheese making takes on a fresh significance in the light of modern stem-cell discoveries. It represents Aristotle's valiant attempt to describe how a featureless gruel of stem cells can manage to organize itself into the mind-boggling complexity of a living creature. And indeed, both curdling and embryogenesis involve complex biochemical cascades that are just waiting to be triggered.

In Aristotle's favor, he often corrected himself and admitted (occasionally) his own ignorance. These endearing qualities made his pronouncements more honest-sounding, and utterly distinct from the certainties of the philosopher kings. In doing so, he was reinforcing the idea that knowledge is not divinely inspired, but rather the result of dedicated research and always subject to review and refinement.

Aristotle's written works were lost to much of the world for centuries, but they were eventually rediscovered by different scholars in Europe, Asia and Africa. In the twelfth century, his works were celebrated by Averroes, a Muslim scholar living in Islamic Spain, and some of his interpretations ultimately worked their way into Islamic theology. That same century, the great Jewish philosopher Maimonides found some success integrating Aristotle into the preachings of the Old Testament, although he would not be as uncritical as Averroes.

In the thirteenth century, Saint Thomas Aquinas would recast much of Christian theology around selected slices of Aristotle's philosophy, namely the Nicomachean Ethics. Unfortunately, Aristotle's democratic and scientific philosophies were deemed too troublesome, and were summarily censored. Aquinas said, "those who use philosophical texts in sacred teaching, by subjugating them to faith, do not mix water with wine, but turn water into wine." After Aristotle was subjugated to faith, only a small drop of old port was left.

Aristotle would have been mortified by how easy it was to wring the science out of his teachings. At various times and in various countries, Aristotle's works were used as a cudgel to enforce conformity. Aristotle's bowdlerized philosophy became one of the greatest noble lies of all. For humanity, it was a long and painful descent from the fledgling scientific and democratic principles first espoused by Aristotle at his cherished Lyceum.

After centuries of suppression, rational, scientific thinking slowly began to reassert itself. The church did its best to harness it, and in fact it ushered in several major breakthroughs in animal husbandry. But the church was losing ground. Its monopolistic grip on research loosened and one prohibition fell after another. Soon, the most forbidden practice of all, human autopsies, became routine. Scientists were determined to overcome nature in order to better the human condition, even in the face of holy wrath.

By the dawn of the seventeenth century, the church had stopped burning scientists at the stake. Slowly but surely science started to recover. By the end of the twentieth century, mankind finally discovered the mysterious stem cells that Aristotle mused about. Let's hope we don't waste another two thousand years figuring out what to do with them.

This is the first installment of a series on the history of cloning and stem-cells. The second article is "A Baby's Hair." Interested in more? Drop me a line!

Copyright © 2000-2014 by Scott Anderson
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Here are some other suggested readings about Aristotle: