The axolotl[1] has the worst luck of any animal I have heard of. This critically endangered salamander has the unfortunate pleasure of living in only two places in the world, Lake Xochimilco and Lake Chalco, two connected lakes in the desert mountains of central Mexico, a dangerous environment for any salamander. The axolotl’s misfortune is compounded by the fact that the Aztecs, guided by ancient prophecy, built their capital, Tenochtitlan, directly on top of the two lakes. Later, after the city was renamed Mexico City, Lake Chalco was drained to prevent flooding, and Lake Xochimilco dammed off into a series of canals, drastically reducing the axolotl’s habitat to a few small, polluted ponds. Even worse, the axolotl is apparently very delicious. It is considered a unique delicacy by the people of Mexico City, various species of fish introduced into the lake, and even other axolotls.
(Fig. 1) – An adult Axolotl. Some claim this creature is adorable. Others claim it is delicious
Misfortune aside, axolotl’s are best known for are their bizarre appearance. The salamander truly deserves it’s name, which translates as “water monster” from Nahuatl, the Aztec language. The axolotl can be anywhere from 6 to 18 inches, varies in color from brown to white, and has a long dorsal fin running the length of its body. Strangest of all, the axolotl has three pairs of external gill stalks attached at the base of the head which absorb oxygen directly from the water. The axolotl’s lungs literally float outside of its body.
Curiously, these external gills are a very common feature among salamander larvae in other species. The gills prevent the salamander larva from venturing on to land and are re-absorbed into the body when the salamander undergoes metamorphosis into a sexually mature adult. The axolotl, unlike many other salamanders, has evolved to retain these external gills throughout its entire life, remaining fully aquatic from life to death. It is an adult juvenile; a sexually mature pre-adolescent salamander.
And though the axolotl lives an unfortunate life, its bizarre appearance points to the deep secret it hides. A secret buried deep within the genetic code which makes this such a fascinating creature. This secret is the reason behind the axolotl’s bizarre and otherworldly appearance, and helps to shed light onto the mysteries of evolution; a secret that ties every single one of us back to the first animals to ever live. This is the secret of the axolotl. Neoteny: a slowing down of development, a process by which an organism slowly evolves to retain juvenile characteristics that were previously discarded, and the genetic foundation that gives rise to such a development.
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Though the axolotl had been known (and eaten) in Mexico since before the arrival of the Europeans, it was not until the 1860’s that the axolotl first came under the lens of scientific research. During the reign of Napoleon III, the resurgent French empire attempted to annex Mexico, stationing armies throughout the country. A scientifically minded army officer, upon seeing the odd looking creatures, sent a shipment back to The Natural History Museum of Paris. There, a group of axolotls made their way into the vivarium of Auguste Henri André Duméril, the museum’s Professor of Herpetology.
Captivated by the new-found species, as anyone would be, Duméril began to study the axolotl, and unwittingly stumbled on to an even more fascinating discovery. While inspecting his vivarium one day, Duméril was shocked to find that a hereto-unknown species of land salamander, in a cage where once there were only aquatic axolotls. Intrigued, and most likely very confused, Duméril began to intensively study the axolotl, and invited other scientists to do the same.
In the course of his research, Duméril came to the conclusion that the axolotl must have transformed, reabsorbing its external gills and shedding the larval characteristics that had before made it so special. For some mysterious reason, it metamorphosed into a salamander that had been lost to time, locked deep within the axolotl’s DNA.
The changed salamander bore such a striking similarity to the Mexican Tiger Salamander that when Duméril published his initial findings, many accused him of stupidly confusing a stow-away tiger salamander for a transformed axolotl. However, as more scientists began to look into this Mexican oddity, they, in true scientific tradition, developed an incredibly strange gambit of experiments to run the poor axolotl through.
One scientist, Marie von Chauvin, began working on the hypothesis that the axolotl’s transformation was induced by the radical differences in environments between Mexico and the museums of Paris. She performed a series of experiments, one of which involved slowly suffocating an axolotl by slowly air-drowning it. Chauvin found that on a regimen of slow, continuous air-drowning would lead an axolotl to transform in a short 7 to 40 weeks.[2]
Chauvin was not alone in her bizarre experiments on the unwitting salamanders. Julian Huxley, Oxford biologist and brother of author Aldus Huxley, put his axolotls on a strict diet of ox thyroid, testing the hypothesis the axolotl’s diet was the major factor, believing that the scarcity of nutrients in Mexico kept the axolotl from transforming. This choice in diet is not as radically strange as you might think. Huxley was actually working off of earlier research that had demonstrated that feeding thyroid to tadpoles led to precocious maturation. Why some scientist had previously decided to feed thyroid to tadpoles though, I haven’t the faintest idea. Luckily, it turned out to be wildly successful. Huxley found that while on this interesting diet, it took the axolotls just over three weeks to fully transform, compared to the agonizingly long time it took the drowning salamanders to transform.
The research that was inspired by the axolotl led to the first formal description of neoteny. Though science lacked the genetic understanding of neoteny[3], it began to be understood as an evolutionary process. And the neotenic axolotl inspired far more than just scientists.
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Julian Huxley was not alone in his family in his love of biology. He was the son of the rabid supporter of Darwinism, Thomas Huxley, who forced an appreciation for in all his children. Julian’s brother, Aldus Huxley, though an author by trade, took a unique fascination in the research that his brother conducted on the axolotl, and was especially enraptured with the concept of neoteny. The idea held fast in his mind, and he began to wonder about the evolution of mankind. He, along with many other people, saw the striking similarity between the young of our closest primate relatives and adult humans. He speculated that humans evolved as neotenic apes, retaining the physical features of young primates while still sexually maturing.
This line of thought was brought forth in Huxley’s novel, After Many a Summer Dies the Swan, largely inspired by his brother’s research. The book revolves around American millionaire Jo Stoyte and his obsessive pursuit of youth and immortality. The hunt to evade the inevitable eventually leads him to the mansion of the Fifth Earl of Gonister, a man of well over two hundred years. The Earl, afraid of death and on a similar mission for immortality, began a diet consisting solely of the eviscerated carp entrails, a plot device almost certainly ripped directly from Julian’s research with ox thyroid. The cost of immortality, as the Earl came to discover, was that as he grew older and older, he began to change. He grew hairier, more brutal, more like an ape, less human day after day. The Earl of Gonister shed his juvenile traits and transformed into the primordial ape locked deep within his genetic code, the same transformation to strike Duméril’s axolotl.
Though the axolotl brought neoteny to the public eye, later research in evolutionary biology has shown that neoteny is a very common evolutionary adaptation. Nearly all salamander species have been known to exhibit neoteny to some degree, some obviously more than others. The axolotl isn’t even unique[4]. Both the Olm, a salamander found in the Balkans, and the American Mudpuppy look eerily similar to the axolotl, exhibiting external gill stalks throughout their fully aquatic life. Some paleontologists even believe that adult birds have many features, such as a large head, eyes, and braincase, which show that modern birds are just tiny, neotenic dinosaurs. Always remember, when you are eating a chicken, you are exacting your ancestor’s long awaited revenge against the mammalian devouring dinosaurs. And though Aldus Huxley’s speculations regarding the neotenic origins of mankind may be slightly off-base, they are not wholly wrong. While it is most likely not true that you will live forever and turn into an ape if you only eat carp guts[5], his intuition was fairly spot on. As later research would show, humans exhibit a number of both physical and behavioral neotenic traits.
The most obvious trait that we seem to have inherited from our juvenile ancestors, and the one that convinced Aldus Huxley of human neoteny, are the similarities between humans and chimpanzees, our closest relative. The classic picture below illustrates how the shape of our skull closely matches that of a baby chimp. Our skulls develop much slower, so by the time we have reached sexual maturity and have stopped growing, our jaw and nose are very slightly extended, while our brain case remains spherical. The adult chimpanzee’s skull develops much quicker, which results in an elongated and flattened shape. Classic neoteny: our development has evolved and slowed down to the point where we stop growing while our skulls still look young.
(Fig. 2) – The skulls of Chimpanzees (Panini Pan) the skulls of humans (Homo Sapiens)
As Harvard Biologist Stephen Jay Gould writes in his book Ontogeny and Phylogeny[6], our neotenic traits extend far beyond simple physical similarities. Both our physical and mental development have evolved to be much slower. We grow and mature as fast as a glacier moves compared to other primates. One theory is that our brain grows very slowly, allowing us to stay in adolescence far beyond the point where other primates would have grown up, moved out, and gotten a job.
Our neotenic development may also be one of the many reasons for the superiority of our species. During childhood, our brain and our neurons can develop synaptic connections that are far more flexible. Developing neotenicly as we do may allow our brain to retain this flexibility, basically throughout our entire lives. We are a learning, curious animal, maybe due to our neotenic evolution. A prolonged adolescence allows our brains to continue growing, which in turn allows us to learn more.
The idea that our neoteny gives us an edge on the harsh realities of existence fits squarely with how all animals evolve. Once again turning to the words of Stephen Jay Gould, evolving neotenic traits was most likely the easiest way for many creatures to ‘escape’ a dangerous situation. Imagine an ancestor of the axolotl, an salamander where the axolotl’s defining features are found only in larvae. For whatever reason, this salamander became trapped in Lake Xochimilco. This would be a disastrous place for a semi-aquatic land salamander to raise a family, and any that wandered too far from the lakes would inevitably suffer either death by eagle, snake, or desert sun.
So the salamanders that were able to stay in the water survived and reproduced more. As the population grew and evolved, salamanders that stopped shedding their lungs lived longer than the salamanders that went on to land. Through natural selection, the neotenic form became the dominant form, and the modern axolotl was born.
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The axolotl, ever the amazing salamander, has yet another secret, one tied intimately to its neoteny and evolution, that sheds light on the interconnectedness of all life on earth. Neoteny, scientifically stated, is a result of changes to the timing of development. Some characteristics develop slowly and some develop quickly. But for a long time, scientists had no idea why. They had no idea why a simple change in timing could result in a salamander with external lungs.
That changed in 1993, when Walter Gehring and Rebecca Quiring, of the University of Basel, published a landmark paper detailing the evolution of the eye and the hierarchal structure of the genetic code. The world had understood the structure of DNA since Watson and Crick discovered the double-helix in 1953, but exactly how genes controlled development was largely unknown, and is still an incredibly important area of modern research.
Individual genes are lazy. They sit in the cell all day, and will do nothing unless a boss tells them to get to work. The bosses, higher-level control genes, tell lower level genes exactly what to do, turning them on and directing their work. These lower level genes will either then turn on other genes or directly code for the creation of a protein, which then tells the cell what to do or how to develop.
The highest-level, master control genes direct entire cascades of genes. Each gene in the cascade can controls for more and more diverse, lower level genes. During development, a few higher level genes will direct how numerous lower level genes interact. Lower level genes, for example, will code for exactly how a structure like an eye will develop, but higher level master control genes will direct and control whether the eye develops or not. Alterations to these higher-level genes cause a huge cascade of changes that magnify and grow; the ‘higher’ the gene in the hierarchy, the more cascading changes. A change higher up in the ladder will cause a whole mess of other changes
Take the PAX6 gene, the master control which Gehring and Quiring discovered is the switch for eyes. While studying a group of fruit flies, they discovered that messing with the PAX6 gene could radically change the development of the eye. A team of scientists at Harvard Medical school, who found a way to directly manipulate the PAX6 gene, decided to test just how powerful this gene was. They found that by turning the gene on and off, they could cause an animal to develop without any eyes at all. By turning off PAX6, they prevented it from telling other genes what to do, which halted the entire cascade, right at the top. The result was not a fly that was blind, but a fly that simply never grew eyes. Without the PAX6 gene, the body just skipped over the development of the eye, as if it was never meant to be there.
In a move that should no longer surprise you, the scientists then decided to do something very, very strange. They decided to turn on PAX6 in a part of the body where an eye would never develop: the leg. After manipulating the proper segments of DNA, they interrupted the development of a leg, forcing the PAX6 gene on. The cells turned to the DNA and waited for instructions. Where before, only the master control gene for legs was active, all of a sudden, so too was PAX6. In addition to the cells being directed to make a leg, they were also being told to start building an eye. And that is just what the cells did. The team of scientists working with PAX6 caused a fly to spontaneously develop a non-functional eye on its leg.
(Fig. 3) See that? That right there is an eye. On a leg.
But the research did not stop there. Another team of researches began doing experiments with the PAX6 gene but in other animals. Eventually the master control gene for eyes was found in mice, and much to the scientists’ surprise, the two genes were 77% similar. And though the two genes were slightly different, it turns out that they coded for the exact same proteins. Though the two control genes were slightly different, they did exactly the same thing.
In an experiment that seems like it came from the annuls of Mad Scientist Monthly, researchers took the master control gene from a mouse, injected it into the DNA of a fly, and waited. As it turns out, injecting the control gene from a mouse caused the fly to grow a fully functional eye. This experiment has been performed countless times, demonstrating that the PAX6 gene from a mouse will cause the development of fly eyes in flies, squid eyes in squid, shark eyes in sharks, and even flatworm eyes in flatworms. All the PAX6 gene does is tell the cell to build an eye. The lower level genes, the ones that actually code for proteins, then tell the cell how to build the right kind of eye.
The amazing fact of the matter is that PAX6 is an incredibly powerful gene that tells the cell to start building an eye, but that seems to be the end of its job. There is an entire cascade of switches and other genes that control the particular intricacies of the eye. The PAX6 looks at the lower level genes, regardless of the animal, and tells them to get to work building an eye. The lowest level genes then look towards mid-level genes, the actual switches, and learn how the eye is to be constructed. In each different animal, there are different switches, each resulting in a different kind of eye.
This is how there can be a common master control gene between such radically different animals. These master control genes are a genetic link to some of the earliest ancestors of all animals throughout history. The original PAX gene most likely evolved around 500 million years ago, and has been passed down through the genetic lineages of millions of different species. The existence and discovery of the PAX gene is one of the strongest indicators that all animal life began evolving from a common ancestor.
It is a fact of evolution that the higher in the hierarchy a gene is, the more resistant it is to change, and the neotenic development of both the axolotl and man-kind are some of the first subtle hints at the extreme power of gene hierarchy. When the axolotl’s environment began selecting for a fully aquatic organism, it was selecting for a gene high up in the hierarchy. As the evolved, its higher-level genes slightly changed, creating a cascading effect, causing the axolotl’s development to halt, allowing it to grow to full maturity while retaining its gill stalks and other juvenile traits.
Humans also harbor these same master control genes. Beating in your heart, and in every cell in your body is a genetic lineage inherited from the ancestor of the mouse, fly, squid, and axolotl. Ever so slight changes to these evolutionary genetic gifts radically changed the timing of our development, which then allowed us to stand up right on the savannahs. The slowing down of our development allowed us to learn, and allowed us to grow beyond the limitations of all other animals. These changes, our neoteny, ties each and every one of us, not only to each other, but by the nature of our genetics, to all other animals on the planet. Without them, without their genes being passed down through time, we would never be here, discovering and delighting in the fascinating secrets of a bizarre Mexican salamander.
But where is our axolotl friend now? Unfortunately, the future of our luckless, strange, and delicious salamander does not look good. In all likelihood, the axolotl will go extinct in the wild within the next few decades as Lake Xochimilco evaporates and the remaining wild axolotls are either killed or eaten. Luckily for us though, the axolotl is quite unlike all those other endangered animals that simply refuse to mate in animal sanctuaries and safe-houses. The axolotl will breed quite happily in captivity, and shall continue to thrive in zoos around the world, unknowingly carrying a secret. A secret of genetics and of evolution, a secret connecting our cute little friend to the billions of other species to have lived and gone extinct. A secret that we too share. Always remember, the secret of the axolotl is your secret too.
[1] Pronounced ack-saw-lah-tuhl
[2] We can now add being slowly suffocated in the name of science to the list of reasons we should be glad that we are not axolotls.
[3] Though DNA was discovered in 1878 by Albrecht Kossel, it was not until 1944 that the Avery–MacLeod–McCarty experiment demonstrated that DNA was the mechanism of heredity
[4] As much as I would like to think that is
[5] I do not know if anyone has actually tried though, so Aldus Huxley may have been right after all
[6] Pronounced ‘On-tah-juh-knee’ and ‘F-eye-lo-juh-knee’, meaning ‘Embryonic Development and Biological Evolution’
Fairly Interesting 