The Human Condition:

Brothers Under the Exoskeleton – December 28, 2014

Fruit fly on a leaf

Anyone who has been following my weekly blogs will know that I am a convinced evolutionist. For ten years I worked at the biotech company that supplied genetic sequencing equipment for the Human Genome Project, DNA analysis tools for forensic and paternity testing, and the machines and reagents for hundreds of other research and clinical applications. I worked alongside chemists, biologists, and engineers and picked their brains whenever I could, as well as doing my own reading on the subject. In later years, it was my job to explain their work and the company’s products to our nontechnical employees as the industry moved from the genome and proteome to the epigenome, the metabolome, and other areas of study, deeper and deeper into life’s molecular secrets.1 From all of this, I know—not just believe, but know—that evolution is the model for the development of life on this planet. It’s literally written into our DNA.

The implication of this is that all life on Earth is related. We share a heritage not just with other mammals but with all the animals and even with plants, bacteria, and fungi. For one example, the DNA/RNA/protein coding system that these organisms use is the same as in our human cells.2 The proof of this is that we can manufacture a human protein in a mammalian or yeast host cell through the process of recombinant DNA. The resulting protein is not “just as good as” the ones made in our own bodies; it is chemically indistinguishable.

For another example, consider our shared structure. You wouldn’t think that an ant and a human have much in common. Apart from the size difference, ants are structured with a tough, inflexible outer shell—an exoskeleton—and hold their organs and other soft parts inside each jointed segment, while we humans have a bony internal skeleton that supports our vital organs by wrapping them in a bag of skin and connective tissue.

But ants and humans, along with every other insect and animal you know—except for worms, jellyfish, and all the radially symmetrical sea life, like sea urchins and octopi—have a common arrangement. We all have a head that encloses our major neural ganglia, or brain. The head also holds our external sensory apparatus for sight, sound, and chemical receptors—that is, our eyes, ears, nose, and tongue—which connect directly to the brain. Further, the head contains our mouth for ingesting food. Human, dog, horse, cow, kangaroo, sloth, dinosaur, reptile, frog, fish, ant, spider, scorpion—we all have this same structural arrangement at what we generally think of as the “top” or “front end” of the body.

After the head comes our thorax, or chest, with the heart, lungs, and other equipment for breathing and circulation. And after the thorax, lower down or toward the rear, comes the abdomen—whether separated by a muscle called the diaphragm in humans and other mammals, reptiles, and amphibians, or by segmentation of body parts in insects. Organs in the abdomen process food, eliminate wastes, and engage in reproduction. Human, dog, dinosaur, fish, spider—all put these functions in more or less the same place.

And while ants may have six legs that grow out of their thorax segment—and spiders the same general arrangement, except with eight legs—we humans along with every other vertebrate animal that walks on land and descended from the line of fishes all have two limbs that grow from shoulderblades attached to the thorax and two limbs that grow from a pelvis attached to the spine near the abdomen. This is the tetrapod—or “four-footed”—super class of animals. Count the front limbs—whether arms, wings, or flippers—and you only come up with two. Count the hind limbs—whether tipped with claws, hooves, or toes—and again only two.3

This is why the chimeras of classical mythology and the medieval bestiaries seem so strange and mysterious. Pegasus has the four legs of a horse plus a pair of wings. Griffins have the wings and legs of an eagle with the hindquarters and tail of a lion. Centaurs have the legs of a horse and the torso of a human. Angels have legs, arms, and wings.4 All of these supposed creatures are six limbed, like the insects, and that violates the tetrapod morphology.

More than this, can we imagine a creature whose mouth was in its stomach? That would make the most sense, wouldn’t it? Give the stomach direct access to the outside world, rather than processing all that bulky food inside the head first and then passing it with a long tube—through the constriction of the neck, which must already contain the spine, muscles, tendons, arteries, and veins supporting the head—down past the heart and lungs and into the abdomen. Or can we imagine a creature with its eyes mounted on stalks alongside or atop its wrists and ankles? That would make controlling the feet in running and the hands doing in close work more convenient, wouldn’t it? We could also look around corners and over windowsills without exposing our fragile faces and heads to surprise attacks and hurled objects.

But these morphological improvements are not the way our bodies work—not in fish, frogs, reptiles, dinosaurs, dogs, or people.

These arrangements go back to an ancient set of genes called the homeobox, which is sometimes shortened to “hox.” These genes don’t code for proteins, because we don’t have a “head” protein or a “chest” protein. Instead they code for “transcription factors,” which are bits of RNA that stay inside the cell’s nucleus and promote other genes during the earliest stages of embryonic development. Hox genes control the cascade of gene activity and the resulting proteins that create our most basic structure.

Animals, plants, and fungi—practically any organism with more than one cell, and so the need to tell each cell in the developing organism where to go and what to become—has a set of hox genes. They are arranged differently and create different structures in animals and plants. But in the blueprint of the final organism, they are the first sketches that set the whole building job into motion.

The hox gene set is remarkably conserved. That means we share a lot of our genes and our resulting structure with most animals but less so with plants.5 Molecular biologists have studied the homeobox gene set most closely in the genus Drosophila, or fruit flies. They have—but did not originate—the same head-with-brain-and-eyes, thorax-with-heart-and-lungs, abdomen-with-stomach-and-reproduction arrangement that fish, frogs, reptiles, and mammals all have.

The interesting thing about fruit flies is that researchers can play with the hox gene set and not get a reprimand from the Society for the Prevention of Cruelty to Animals—that, and the flies breed new generations relatively fast, so you can study changes on a convenient time scale. What we’ve learned is that if you mutate these genes, or silence them, you can change the animal’s structure. You can breed fruit flies with legs growing where their antenna should be, or with eyes in the middle of their wings. Of course, if you change the number and arrangement of these genes too much—say, trying to place the head between the thorax and the abdomen—you simply kill the embryonic fly by creating a totally scrambled, nonviable structure.

The fact that we share so many proteins, so many of the genes that make them, and the genes that create our basic structures with other animals—and the DNA/RNA system that records and transmits all this with all other life on Earth—is proof enough to me that we are all related. And that relationship is mediated by gradual adaptation through many generations. The foreleg of the early tetrapod changes and adapts over time to become the wing of a bird or bat, the leg of a horse or cat, or the grasping hand of a monkey or a man. The compound, prismatic eye of the fruit fly occupies the same position in the head as the single-focal-plane, liquid eye of the horse or the human.

We are all brothers under the exoskeleton.

1. What are all these “omes”? In current molecular biology, an “ome” is the domain of a particular system under study. The genome is concerned with the operation of the genes: the DNA/RNA system. The proteome is the study of proteins and their interactions. The epigenome concerns itself with environmental and chemical effects that modify DNA expression. And the metabolome deals with the metabolism, its inputs and products, on either the cellular or bodily level. The field of molecular biology is widening all the time and simultaneously becoming intertwined, as researchers explore and link up all these different pathways and their effect upon one another.

2. With minor mechanical exceptions. For example, the ribosome—the RNA-based molecule which translates the coding of messenger RNA to assemble amino acids in making the body’s proteins—differs between eukaryotes (multi-celled organisms whose DNA sits inside a nucleus) and prokaryotes (single-celled organisms whose DNA floats around in the cell). Almost all antibiotics work to inhibit the operation of the ribosomes in prokaryotes but not in eukaryotes—which is why they kill the bacteria inside our bodies but not us or our livestock and plants. This is also why antibiotics won’t protect you from a virus, because viruses hijack the host’s genetic system to transcribe and translate their DNA.

3. But what about whales and dolphins? They descended from land animals that went back into the sea, and they have no legs. Neither do snakes. But these animals generally have vestigial hips and leg bones hidden inside their bodies. Even if they don’t use them, the genes for these features remain to make themselves felt. And of course, the tails of whales and dolphins are a different, boneless appendage not related to the organism’s skeletal structure.

4. How does the musculature of the angel’s human-appearing upper arm and shoulder cross over and coincide with the musculature of its birdlike wing? And which muscle system dominates the mechanics of the shoulderblade? It’s all a mystery.

5. Consider that most plants have their food-processing organs in their deep roots, their reproductive organs in their flowering tops, their lungs in their leaves, no hearts to speak of, because they rely on capillary action to pass fluids up and down, and no need for legs, because they spend their adult lives in one spot.. They all share a homeobox organization that is just downright alien compared with that of mice and men.