Our Own Body Of Evidence

A photo could never capture just how much of our bodies is to be found within those Precambrian disks, fronds, and ribbons. What could we humans, with all our complexity, ever share with impressions in rocks, particularly ones that look like crinkled jellyfish and squashed rolls of film?

The answer is profound and, when we see the evidence, inescapable: the "stuff' that holds us together—that makes our bodies possible—is no different from what formed the bodies of Gurich's and Sprigg's ancient impressions. In fact, the scaffolding of our entire body originated in a surprisingly ancient place: single-celled animals.

What holds a clump of cells together, whether they form a jellyfish or an eyeball? In creatures like us, that biological glue is astoundingly complicated; it not only holds our cells together, but also allows cells to communicate and forms much of our structure. The glue is not one thing; it is a variety of different molecules that connect and lie between our cells. At the microscopic level, it gives each of our tissues and organs its distinctive appearance and function. An eyeball looks different from a leg bone whether we look at it with the naked eye or under a microscope. In fact, much of the difference between a leg bone and an eye rests in the ways the cells and materials are arranged deep inside.

Every fall for the past several years, I have driven medical students crazy with just these concepts. Nervous first-year students must learn to identify organs by looking at random slides of tissue under a microscope. How do they do this?

The task is a little like figuring out what country you are in by looking at a street map of a small village. The task is doable, but we need the right clues. In organs, some of the best clues lie in the shape of cells and how they attach to one another; it is also important to be able to identify the stuff that lies between them. Tissues have all kinds of different cells, which attach to one another in different ways: some regions have strips or columns of cells; in others, cells are randomly scattered and loosely attached to one another. These areas, where cells are loosely packed, are often filled with materials that give each tissue its characteristic physical properties. For instance, the minerals that lie between bone cells determine the hardness of bone, whereas the looser proteins in the whites of our eyes make the wall of the eyeball more pliant.

Our students' ability to identify organs from microscope slides, then, comes from knowing how cells are arranged and what lies between the cells. For us, there is a deeper meaning. The molecules that make these cellular arrangements possible are the molecules that make bodies possible. If there were no way to attach cells to one another, or if there were no materials between cells, there would be no bodies on the earth—just batches of cells. This means that the starting point for understanding how and why bodies arose is to see these molecules: the molecules that help cells stick together, the molecules that allow them to communicate with one another, and the substances that lie between cells.

To understand the relevance of this molecular structure to our bodies, let's focus in detail on one part: our skeleton. Our skeleton is a powerful example of how tiny molecules can have a big impact on the structure of our body and exemplifies general principles that apply to all the body's parts. Without skeletons, we would be formless masses of goo. Living on land would not be easy or even possible. So much of our basic biology and behavior is made possible by our skeleton that we often take it for granted. Every time we walk, play piano, inhale, or chew food we have our skeleton to thank.

A great analogy for the workings of our skeleton is a bridge. The strength of a bridge depends on the sizes, shapes, and proportions of its girders and cables. But also, importantly, the strength of the bridge depends on the microscopic properties of the materials from which it is made. The molecular structure of steel determines how strong it is and how far it will bend before breaking. In the same way, our skeleton's strength is based on the sizes and shapes of our bones, but also on the molecular properties of our bones themselves.

Let's go for a run to see how. As we jog along a path, our muscles contract, our back, arms, and legs move, and our feet push against the ground to move us forward. Our bones and joints function like a giant complex of levers and pulleys that make all that movement possible. Our body's movements are governed by basic physics: our ability to run is in large part based on the size, shape, and proportions of our skeleton and the configuration of our joints. At this level, we look like a big machine. And like a machine, our design matches our functions. A world-class high jumper has different bone proportions from a champion sumo wrestler. The proportions of the legs of a rabbit or a frog, specialized to hop and jump, are different from those of a horse.

Now, let's take a more microscopic view. Pop a slice of a femur under the microscope, and you will immediately see what gives bone its distinctive mechanical properties. The cells are highly organized in places, particularly on the outer rim of the bone. Some cells stick together, whereas others are separated. Between the separated cells are the materials that define the strength of bone. One of them is the rock, or crystal, known as hydroxyapatite, which we discussed in Chapter 4. Hydroxyapatite is hard the way concrete is: strong when compressed, less strong if twisted or bent. So, like a building made of bricks or concrete, bones are shaped so as to maximize their compressive functions and minimize twisting and bending, something Galileo recognized in the seventeenth century.

The other molecule found between our bone cells is the most common protein in the entire human body. If we magnify it 10,000 times with an electron microscope, we see something that looks like a rope consisting of bundles of little molecular fibers. This molecule, collagen, also has the mechanical properties of a rope. Rope is relatively strong when pulled, but it collapses when compressed; think of the two teams in a tug-of-war running toward the middle. Collagen, like rope, is strong when pulled but weak when the ends are pushed together.

Bone is composed of cells that sit in a sea of hydroxyapatite, collagen, and some other, less common molecules. Some cells stick together; other cells float inside these materials. The strength of bone is based on collagen's strength when pulled, and on hydroxyapatite's strength when compressed.

Cartilage, the other tissue in our skeleton, behaves somewhat differently. During our jog, it was the cartilage in our joints that provided the smooth surfaces where our bones glided against one another. Cartilage is a much more pliant tissue than bone; it can bend and smush as forces are applied to it. The smooth operation of the knee joint, as well as most of the other joints we used during our jog, depends on having relatively soft cartilage. When healthy cartilage is compressed it always returns to its native shape, like a kitchen sponge. During each step of our run, our entire body mass slams against the ground at some speed. Without these protective caps at our joints our bones would grind against one another: a very unpleasant and debilitating outcome of arthritis.

The pliability of cartilage is a property of its microscopic structure. The cartilage at our joints has relatively few cells, and these cells are separated by a lot of filling between them. As with bone, it is the properties of this interstitial filling that largely determine the mechanical properties of the cartilage.

Collagen fills much of the space between cartilage cells (as well as the cells of our other tissues). What really gives cartilage its pliancy is another kind of molecule, one of the most extraordinary in the whole body. This kind of molecule, called a proteoglycan complex, gives cartilage strength when squeezed or compressed. Shaped like a giant three-dimensional brush, with a long stem and lots of little branches, the proteoglycan complex is actually visible under a microscope. It has an amazing property relevant to our abilities to walk and move, thanks to the fact that the tiniest branches love to attach to water. A proteoglycan, then, is a molecule that actually swells up with water, filling up until it's like a giant piece of Jell-O. Take this piece of gelatin, wrap collagen ropes in and around it, and you end up with a substance that is both pliant and somewhat resistant to tension. This, essentially, is cartilage. A perfect pad for our joints. The role of the cartilage cells is to secrete these molecules when the animal is growing and maintain them when the animal is not.

The ratios among the various materials define much of the mechanical differences among bone, cartilage, and teeth. Teeth are very hard and, predictably, there is lots of hydroxyapatite and relatively little collagen between the cells in the enamel. Bone has relatively more collagen, less hydroxyapatite, and no enamel. Consequently, it is not as hard as teeth. Cartilage has lots of collagen and no hydroxyapatite, and is loaded with proteoglycans. It is the softest of the tissues in our skeleton. One of the main reasons our skeletons look and work as they do is that these molecules are deployed in the right places in the right proportions.

What does all this have to do with the origin of bodies? One property is common to animals, whether they have skeletons or not: all of them, including clumps of cells, have molecules that lie between their cells, specifically different kinds of collagens and proteoglycans. Collagen seems particularly important: the most common protein in animals, it makes up over 90 percent of the body's protein by weight. Bodybuilding in the distant past meant that molecules like these had to be invented.

Something else is essential for bodies: the cells in our bones have to be able to stick together and talk to one another. How do bone cells attach to one another, and how do different parts of bone know to behave differently? Here is where much of our bodybuilding kit lies.

Bone cells, like every cell in our bodies, stick to one another by means of tiny molecular rivets, of which there is a vast diversity. Some bind cells the way contact cement holds the soles of shoes together: one molecule is firmly attached to the outer membrane of one cell, another to the outer membrane of a neighboring cell. Thus attached to both cell membranes, the glue forms a stable bond between the cells.

Other molecular rivets are so precise that they bind selectively, only to the same kind of rivet. This is a hugely significant feature because it helps organize our bodies in a fundamental way. These selective rivets enable cells to organize themselves and ensure that bone cells stick to bone cells, skin to skin, and so on. They can organize our bodies in the absence of other information. If we put a number of cells, each with a different kind of this type of rivet, on a dish and let the cells grow, the cells will organize themselves. Some might form balls, others sheets, as the cells sort out by the numbers and kinds of rivets they have.

But arguably the most important connection between cells lies in the ways that they exchange information with one another. The precise pattern of our skeleton, in fact of our whole body, is possible only because cells know how to behave. Cells need to know when to divide, when to make molecules, and when to die. If, for example, bone or skin cells behaved randomly—if they divided too much or died too little—then we would be very ugly or, worse, very dead.

Cells communicate with one another using "words" written as molecules that move from cell to cell. One cell can "talk" to the next by sending molecules back and forth. For instance, in a relatively simple form of cell-to-cell communication, one cell will emit a signal, in this case a molecule. This molecule will attach to the outer covering, or membrane, of the cell receiving the signal. Once attached to the outer membrane, the molecule will set off a chain reaction of molecular events that travels from the outer membrane all the way, in many cases, to the nucleus of the cell. Remember that the genetic information sits inside the nucleus. Consequently, this molecular signal can cause genes to be turned on and off. The end result of all this is that the cell receiving the information now changes its behavior: it may die, divide, or make new molecules in response to the cue from the other cell.

At the most basic level, these are the things that make bodies possible. All animals with bodies have structural molecules like collagens and proteoglycans, all of them have the array of molecular rivets that hold cells together, and all of them have the molecular tools that allow cells to communicate with one another.

We now have a search image to understand the how of body origins. To see how bodies arose, we need to look for these molecules in the most primitive bodies on the planet, and then, ultimately, in creatures that have no body at all.

0 0

Post a comment