Your Inner Fish: A Journey Into the 3.5-Billion-Year History of the Human Body

by Neil Shubin

  For that find, we had to search almost ten years. And I wasn’t the first to recognize what we were looking at. The first were two professional fossil preparators, Fred Mullison and Bob Masek. Preparators use dental tools to scratch at the rocks we find in the field and thereby expose the fossils inside. It can take months, if not years, for a preparator to turn a big fossil-filled boulder like ours into a beautiful, research-quality specimen.

  During the 2004 expedition, we had collected three chunks of rock, each about the size of a piece of carry-on luggage, from the Devonian of Ellesmere Island. Each contained a flat-headed animal: the one I found in ice at the bottom of the quarry, Steve’s specimen, and a third specimen we discovered in the final week of the expedition. In the field we had removed each head, leaving enough rock intact around it to explore in the lab for the rest of the body. Then the rocks were wrapped in plaster for the trip home. Opening these kinds of plaster coverings in the lab is much like encountering a time capsule. Bits and pieces of our life on the Arctic tundra are there, as are the field notes and scribbles we make on the specimen. Even the smell of the tundra comes wafting out of these packages as we crack the plaster open.

  Fred in Philadelphia and Bob in Chicago were scratching on different boulders at the same general time. From one of these Arctic blocks, Bob had pulled out a particular small bone in a big fin of the Fish (we hadn’t named it Tiktaalik yet). What made this cube-shaped blob of bone different from any other fin bone was a joint at the end that had spaces for four other bones. That is, the blob looked scarily like a wrist bone—but the fins in the block that Bob was preparing were too jumbled to tell for sure. The next piece of evidence came from Philadelphia a week later. Fred, a magician with his dental tools, uncovered a whole fin in his block. At the right place, just at the end of the forearm bones, the fin had that bone. And that bone attached to four more beyond. We were staring at the origin of a piece of our own bodies inside this 375-million-year-old fish. We had a fish with a wrist.

  The bones of the front fin of Tiktaalik— a fish with a wrist.

  Over the next months, we were able to see much of the rest of the appendage. It was part fin, part limb. Our fish had fin webbing, but inside was a primitive version of Owen’s one bone–two bones–lotsa blobs–digits arrangement. Just as Darwin’s theory predicted: at the right time, at the right place, we had found intermediates between two apparently different kinds of animals.

  Finding the fin was only the beginning of the discovery. The real fun for Ted, Farish, and me came from understanding what the fin did and how it worked, and in guessing why a wrist joint arose in the first place. Solutions to these puzzles are found in the structure of the bones and joints themselves.

  When we took the fin of Tiktaalik apart, we found something truly remarkable: all the joint surfaces were extremely well preserved. Tiktaalik has a shoulder, elbow, and wrist composed of the same bones as an upper arm, forearm, and wrist in a human. When we study the structure of these joints to assess how one bone moves against another, we see that Tiktaalik was specialized for a rather extraordinary function: it was capable of doing push-ups.

  When we do push-ups, our hands lie flush against the ground, our elbows are bent, and we use our chest muscles to move up and down. Tiktaalik’s body was capable of all of this. The elbow was capable of bending like ours, and the wrist was able to bend to make the fish’s “palm” lie flat against the ground. As for chest muscles, Tiktaalik likely had them in abundance. When we look at the shoulder and the underside of the arm bone at the point where they would have connected, we find massive crests and scars where the large pectoral muscles would have attached. Tiktaalik was able to “drop and give us twenty.”

  A full-scale model of Tiktaalik’s body (top) and a drawing of its fin (bottom). This is a fin in which the shoulder, elbow, and proto-wrist were capable of performing a type of push-up.

  Why would a fish ever want to do a push-up? It helps to consider the rest of the animal. With a flat head, eyes on top, and ribs, Tiktaalik was likely built to navigate the bottom and shallows of streams or ponds, and even to flop around on the mudflats along the banks. Fins capable of supporting the body would have been very helpful indeed for a fish that needed to maneuver in all these environments. This interpretation also fits with the geology of the site where we found the fossils of Tiktaalik. The structure of the rock layers and the pattern of the grains in the rocks themselves have the characteristic signature of a deposit that was originally formed by a shallow stream surrounded by large seasonal mudflats.

  But why live in these environments at all? What possessed fish to get out of the water or live in the margins? Think of this: virtually every fish swimming in these 375-million-year-old streams was a predator of some kind. Some were up to sixteen feet long, almost twice the size of the largest Tiktaalik. The most common fish species we find alongside Tiktaalik is seven feet long and has a head as wide as a basketball. The teeth are barbs the size of railroad spikes. Would you want to swim in these ancient streams?

  It is no exaggeration to say that this was a fish-eat-fish world. The strategies to succeed in this setting were pretty obvious: get big, get armor, or get out of the water. It looks as if our distant ancestors avoided the fight.

  But this conflict avoidance meant something much deeper to us. We can trace many of the structures of our own limbs to the fins of these fish. Bend your wrist back and forth. Open and close your hand. When you do this, you are using joints that first appeared in the fins of fish like Tiktaalik. Earlier, these joints did not exist. Later, we find them in limbs.

  Proceed from Tiktaalik to amphibians all the way to mammals, and one thing becomes abundantly clear: the earliest creature to have the bones of our upper arm, our forearm, even our wrist and palm, also had scales and fin webbing. That creature was a fish.

  What do we make of the one bone–two bones–lotsa blobs–digits plan that Owen attributed to a Creator? Some fish, for example the lungfish, have the one bone at the base. Other fish, for example Eusthenopteron, have the one bone–two bones arrangement. Then there are creatures like Tiktaalik, with one bone–two bones–lotsa blobs. There isn’t just a single fish inside of our limbs; there is a whole aquarium. Owen’s blueprint was assembled in fish.

  Tiktaalik might be able to do a push-up, but it could never throw a baseball, play the piano, or walk on two legs. It is a long way from Tiktaalik to humanity. The important, and often surprising, fact is that most of the major bones humans use to walk, throw, or grasp first appear in animals tens to hundreds of millions of years before. The first bits of our upper arm and leg are in 380-million-year-old fish like Eusthenopteron. Tiktaalik reveals the early stages in the evolution of our wrist, palm, and finger area. The first true fingers and toes are seen in 365-million-year-old amphibians like Acanthostega. Finally, the full complement of wrist and ankle bones found in a human hand or foot is seen in reptiles more than 250 million years old. The basic skeleton of our hands and feet emerged over hundreds of millions of years, first in fish and later in amphibians and reptiles.

  But what are the major changes that enable us to use our hands or walk on two legs? How do these shifts come about? Let’s look at two simple examples from limbs for some answers.

  We humans, like many other mammals, can rotate our thumb relative to our elbow. This simple function is very important for the use of our hands in everyday life. Imagine trying to eat, write, or throw a ball without being able to rotate your hand relative to your elbow. We can do this because one forearm bone, the radius, rotates along a pivot point at the elbow joint. The structure of the joint at the elbow is wonderfully designed for this function. At the end of our upper-arm bone, the humerus, lies a ball. The tip of the radius, which attaches here, forms a beautiful little socket that fits on the ball. This ball-and-socket joint allows the rotation of our hand, called pronation and supination. Where do we see the beginnings of this ability? In creatures like Tiktaalik. In Tiktaalik, the end of the humerus
forms an elongated bump onto which a cup-shaped joint on the radius fits. When Tiktaalik bent its elbow, the end of its radius would rotate, or pronate, relative to the elbow. Refinements of this ability are seen in amphibians and reptiles, where the end of the humerus becomes a true ball, much like our own.

  Looking now at the hind limb, we find a key feature that gives us the capacity to walk, one we share with other mammals. Unlike fish and amphibians, our knees and elbows face in opposite directions. This feature is critical: think of trying to walk with your kneecap facing backward. A very different situation exists in fish like Eusthenopteron, where the equivalents of the knee and elbow face largely in the same direction. We start development with little limbs oriented much like those in Eusthenopteron, with elbows and knees facing in the same direction. As we grow in the womb, our knees and elbows rotate to give us the state of affairs we see in humans today.

  Our bipedal pattern of walking uses the movements of our hips, knees, ankles, and foot bones to propel us forward in an upright stance unlike the sprawled posture of creatures like Tiktaalik. One big difference is the position of our hips. Our legs do not project sideways like those of a crocodile, amphibian, or fish; rather, they project underneath our bodies. This change in posture came about by changes to the hip joint, pelvis, and upper leg: our pelvis became bowl shaped, our hip socket became deep, our femur gained its distinctive neck, the feature that enables it to project under the body rather than to the side.

  Do the facts of our ancient history mean that humans are not special or unique among living creatures? Of course not. In fact, knowing something about the deep origins of humanity only adds to the remarkable fact of our existence: all of our extraordinary capabilities arose from basic components that evolved in ancient fish and other creatures. From common parts came a very unique construction. We are not separate from the rest of the living world; we are part of it down to our bones and, as we will see shortly, even our genes.

  In retrospect, the moment when I first saw the wrist of a fish was as meaningful as the first time I unwrapped the fingers of the cadaver back in the human anatomy lab. Both times I was uncovering a deep connection between my humanity and another being.

  CHAPTER THREE

  HANDY GENES

  While my colleagues and I were digging up the first Tiktaalik in the Arctic in July 2004, Randy Dahn, a researcher in my laboratory, was sweating it out on the South Side of Chicago doing genetic experiments on the embryos of sharks and skates, cousins of stingrays. You’ve probably seen small black egg cases, known as mermaid’s purses, on the beach. Inside the purse once lay an egg with yolk, which developed into an embryonic skate or ray. Over the years, Randy has spent hundreds of hours experimenting with the embryos inside these egg cases, often working well past midnight. During the fateful summer of 2004, Randy was taking these cases and injecting a molecular version of vitamin A into the eggs. After that he would let the eggs develop for several months until they hatched.

  His experiments may seem to be a bizarre way to spend the better part of a year, let alone for a young scientist to launch a promising scientific career. Why sharks? Why a form of vitamin A?

  To make sense of these experiments, we need to step back and look at what we hope they might explain. What we are really getting at in this chapter is the recipe, written in our DNA, that builds our bodies from a single egg. When sperm fertilizes an egg, that fertilized egg does not contain a tiny hand, for instance. The hand is built from the information contained in that single cell. This takes us to a very profound problem. It is one thing to compare the bones of our hands with the bones in fish fins. What happens if you compare the genetic recipe that builds our hands with the recipe that builds a fish’s fin? To find answers to this question, just like Randy, we will follow a trail of discovery that takes us from our hands to the fins of sharks and even to the wings of flies.

  As we’ve seen, when we discover creatures that reveal different and often simpler versions of our bodies inside their own, a wonderfully direct window opens into the distant past. But there is a big limitation to working with fossils. We cannot do experiments on long-dead animals. Experiments are great because we can actually manipulate something to see the results. For this reason, my laboratory is split directly in two: half is devoted to fossils, the other half to embryos and DNA. Life in my lab can be schizophrenic. The locked cabinet that holds Tiktaalik specimens is adjacent to the freezer containing our precious DNA samples.

  Experiments with DNA have enormous potential to reveal inner fish. What if you could do an experiment in which you treated the embryo of a fish with various chemicals and actually changed its body, making part of its fin look like a hand? What if you could show that the genes that build a fish’s fin are virtually the same as those that build our hands?

  We begin with an apparent puzzle. Our body is made up of hundreds of different kinds of cells. This cellular diversity gives our tissues and organs their distinct shapes and functions. The cells that make our bones, nerves, guts, and so on look and behave entirely differently. Despite these differences, there is a deep similarity among every cell inside our bodies: all of them contain exactly the same DNA. If DNA contains the information to build our bodies, tissues, and organs, how is it that cells as different as those found in muscle, nerve, and bone contain the same DNA?

  The answer lies in understanding what pieces of DNA (the genes) are actually turned on in every cell. A skin cell is different from a neuron because different genes are active in each cell. When a gene is turned on, it makes a protein that can affect what the cell looks like and how it behaves. Therefore, to understand what makes a cell in the eye different from a cell in the bones of the hand, we need to know about the genetic switches that control the activity of genes in each cell and tissue.

  Here’s the important fact: these genetic switches help to assemble us. At conception, we start as a single cell that contains all the DNA needed to build our body. The plan for that entire body unfolds via the instructions contained in this single microscopic cell. To go from this generalized egg cell to a complete human, with trillions of specialized cells organized in just the right way, whole batteries of genes need to be turned on and off at just the right stages of development. Like a concerto composed of individual notes played by many instruments, our bodies are a composition of individual genes turning on and off inside each cell during our development.

  Genes are stretches of DNA contained in every cell of our bodies.

  This information is a boon to those who work to understand bodies, because we can now compare the activity of different genes to assess what kinds of changes are involved in the origin of new organs. Take limbs, for example. When we compare the ensemble of genes active in the development of a fish fin to those active in the development of a human hand, we can catalogue the genetic differences between fins and limbs. This kind of comparison gives us some likely culprits—the genetic switches that may have changed during the origin of limbs. We can then study what these genes are doing in the embryo and how they might have changed. We can even do experiments in which we manipulate the genes to see how bodies actually change in response to different conditions or stimuli.

  To see the genes that build our hands and feet, we need to take a page from a script for the TV show CSI: Crime Scene Investigation—start at the body and work our way in. We will begin by looking at the structure of our limbs, and zoom all the way down to the tissues, cells, and genes that make it.

  MAKING HANDS

  Our limbs exist in three dimensions: they have a top and a bottom, a pinky side and a thumb side, a base and a tip. The bones at the tips, in our fingers, are different from the bones at the shoulder. Likewise, our hands are different from one side to the other. Our pinkies are shaped differently from our thumbs. The Holy Grail of our developmental research is to understand what genes differentiate the various bones of our limb, and what controls development in these three dimensions. What DNA actually makes a pinky di
fferent from a thumb? What makes our fingers distinct from our arm bones? If we can understand the genes that control such patterns, we will be privy to the recipe that builds us.

  All the genetic switches that make fingers, arm bones, and toes do their thing during the third to eighth week after conception. Limbs begin their development as tiny buds that extend from our embryonic bodies. The buds grow over two weeks, until the tip forms a little paddle. Inside this paddle are millions of cells which will ultimately give rise to the skeleton, nerves, and muscles that we’ll have for the rest of our lives.

  The development of a limb, in this case a chicken wing. All of the key stages in the development of a wing skeleton happen inside the egg.

  To study how this pattern emerges, we need to look at embryos and sometimes interfere with their development to assess what happens when things go wrong. Moreover, we need to look at mutants and at their internal structures and genes, often by making whole mutant populations through careful breeding. Obviously, we cannot study humans in these ways. The challenge for the pioneers in this field was to find the animals that could be useful windows into our own development. The first experimental embryologists interested in limbs in the 1930s and 1940s faced several problems. They needed an organism in which the limbs were accessible for observation and experiment. The embryo had to be relatively large, so that they could perform surgical procedures on it. Importantly, the embryo had to grow in a protected place, in a container that sheltered it from jostling and other environmental disturbances. Also, and critically, the embryos had to be abundant and available year-round. The obvious solution to this scientific need is at your local grocery store: chicken eggs.