Your Inner Fish: A Journey Into the 3.5-Billion-Year History of the Human Body (7 page)

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

W
hile 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 different 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.