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Brutes or Angels
HUMAN POSSIBILITY IN THE AGE OF BIOTECHNOLOGY
By James T. Bradley
THE UNIVERSITY OF ALABAMA PRESS Copyright © 2013The University of Alabama Press
All rights reserved.
Cells and molecules
The Unity of life
long ago it became evident that the key to every biological problem must finally be sought in the cell; for every living organism is, or at sometime has been, a cell.
—edmond B. Wilson, The Cell in Development and Heredity (Genes, Cells, and Organisms)
on August 20, 1979, Newsweek magazine sported a cover with a beautiful color cartoon of a single cell and its interior. This and the accompanying story, "secrets of the human Cell," illustrated the prominence and relevance of cell biology for the general public that was evident more than thirty years ago. Since then, discoveries in cell biology and biotechnology have given rise to the so-called new biology that increasingly influences how we are conceived, how we live, and when we die.
Cells comprise our bodies; cells, in turn, are comprised of chemical units called molecules. Why does knowing about cells and molecules matter? every biotechnology discussed in this book, from stem cells and cloning to genetic enhancement and age retardation, has its foundation in cellular and molecular biology. Quite literally, cells are us. We are made of cells, some twelve trillion of them. Not only do cells comprise or manufacture all the parts of our physical bodies, but they also make us thinking, rational, even spiritual beings. Writing about the 100 trillion cell-to-cell communication sites (synapses) inside the human brain, neuroscientist Joseph LeDoux (2002, ix) puts it this way, "you are your synapses.... They are the channels of communication between brain cells, and the means by which most of what the brain does is accomplished."
As we learn more and more about cells and the chemistry of life, we gain correspondingly more opportunities to biologically alter ourselves and the rest of the living world. Reshaping life wisely requires biologically literate non-biologists to make decisions about how biotechnologies are developed and used. This is why knowing about cells and molecules matters. Moreover, learning about the beauty of life beyond what our unaided eyes can see is fun. And life should be fun. So let's get started and jump right into the world of the cell. The following questions will guide our foray into the microscopic and submicroscopic realms of biology:
1. What are cells and molecules?
2. What do cell biologists do?
3. How is cell structure related to cell function?
4. What are the relationships between DNA, genes, chromosomes, and genomes?
5. What is the central dogma of biology?
6. What is the genetic code?
7. How do cells reproduce?
8. When and how did the first cells originate?
9. What do cells have to do with human values?
Cells and molecules
Just as different types of buildings are units of a city, cells are the structural and functional units of all living things on Earth. But unlike buildings, all cells come from pre-existing cells. Together, these two statements about cells constitute the "cell theory." The first, that all living things are comprised of cells, was proposed for plants in 1838 by a German botanist, Matthias Schleiden, and for animals in 1839 by Schleiden's zoologist colleague, Theodor Schwann. The second statement, that only cells beget cells, was proposed in 1855 by the German pathologist Rudolf Virchow. Direct observations and experimental data soon elevated the original propositions of Schleiden, Schwann, and Virchow to the level of theory, with a certainty comparable to that enjoyed by the heliocentric theory for the solar sys tem and the germ theory for disease. The two components of the cell theory have now been established principles of biology for 150 years.
Broadly speaking, there are two kinds of cells: prokaryotic and eukaryotic. Prokaryotic cells include bacteria and some types of algae. In the late 1970s, prokaryotic cells were divided into two major groups based on biochemical and genetic characteristics. So now biologists recognize three kingdoms of cells: Eukarya, Bacteria, and Archaea (fig. 1.1), the latter two kingdoms being prokaryotic. Bacteria include the familiar beneficial and disease-causing microbes that live in our gut, grow in the soil, give us infections, or cause Lyme disease. Archaea live in extreme environments like the hot springs in Yellowstone National Park and in places with high salt or methane levels. Eukarya include organisms from amoebae and armadillos to mushrooms, mimosa trees, mountain lions, and humans, all comprised of eukaryotic cells.
You may wonder how viruses fit into this cell classification scheme. They do not! viruses are not alive, and they are not cells. Viruses can cause havoc inside cells by commandeering life's normal processes and subverting them toward propagating more virus particles. Most of this book is about eukaryotic cells, discoveries about how they work, and technologies we can use to manipulate them to do our bidding.
What about molecules? Molecules are atoms bonded together into stable configurations. They are all around us in the biological and non-biological worlds. Teflon and nylon are man-made molecules. DNA and proteins are examples of nature's molecules, but they too can be made by humans. DNA and proteins are at the core of life itself. DNA is the cell's hereditary material, and it carries the information needed for the cell to make proteins. Proteins are directly or indirectly responsible for virtually all of the parts of a cell and their various functions. We explore these two types of molecules further later on in this chapter.
Chemists and biologists diagram molecules to show how the atoms are bonded to each other (fig. 1.2). For example, a water molecule contains one oxygen atom (O) and two hydrogen (H) atoms, which is why we designate water as H2O. Similarly, the blood sugar, glucose, contains six carbon (C) atoms, twelve h atoms, six O atoms and is designated C6H12O6. DNA and proteins are very large molecules, containing thousands of atoms.
To sum up, atoms comprise molecules, molecules form cells, ordered arrays of cells form tissues and organs, and organ systems cooperate to sustain organisms. The most common atoms in biological molecules are C, O, and H. Other important but less common atoms in biological molecules are phosphorus (P), nitrogen (N), sulfur (S), and iron (Fe). Many trace elements are also important to cells. Some of these are in the ingredients list on your bottle of multivitamins.
What Do Cell Biologists Do?
Cell biologists are "renaissance" scientists. They draw upon methods and findings from a variety of sources and integrate these into the relatively young discipline called cell biology. Information from genetics (study of heredity), cytology (study of cell structure), biochemistry (chemistry of life), physics (study of energy and matter), and molecular biology (study of DNA function) contributes to the cell biologist's understanding of how a cell works.
Sometimes cell biologists focus on the very small, like the shape or function of specific molecules inside a cell, and other times they take a panoramic view of cells and examine how the shapes, spatial arrangements, and communication between millions and billions of cells produce functioning tissues and organs. In the end, a cell biologist's goal is to explore the relationship between the structure and function of cells and their parts.
Cell biology emerged as a discipline during the early 1960s due to two new technologies: biological transmission electron microscopy (TEM) and high-speed centrifugation. TEM (fig. 1.3, bottom) allowed the structures of very small components of cells to be seen either for the first time or in much greater detail than previously using conventional light microscopy (fig. 1.3, top). When high school biology students use light microscopes to examine drops of pond scum for microscopic life, they see objects 500 times smaller than those visible to the unaided human eye. TEM can visualize objects 250 times smaller than those seen with the best light microscope; that is, TEM can show us subcellular structures whose sizes correspond roughly to the width of a DNA molecule.
High-speed centrifugation of cell homogenates (mixtures of the contents of purposefully ruptured cells suspended in solution) allowed biologists to isolate purified, subcellular components called organelles (little organs). Soon biochemists began learning about the biochemical functions performed by each type of organelle. Discoveries made possible by TEM and high-speed centrifugation, laboratory methods still widely used, gave birth to a new discipline focused on the relationship between subcellular structure and biochemical function, cell biology.
Cell structure and function
Before the rise of molecular biology in the 1970s, biologists used structural criteria to classify cells as either prokaryotic or eukaryotic. Eukaryotic cells possess a true, membrane-bound nucleus (eu = true; karyon = nucleus) easily visible by light microscopy as a roughly spherical object comprising about one-third of the cell's volume. The nucleus contains DNA and an array of proteins that facilitate DNA's function as the hereditary material. The non-nuclear region of the cell is called the cytoplasm. Prokaryotic cells lack a true nucleus (pro = before; karyon = nucleus), so the genetic material resides in the cytoplasm along with other cellular constituents. The word prokaryotic, "before a nucleus," describes cells that appeared on the earth before eukaryotic cells.
The nucleus is the most prominent structure inside eukaryotic cells. It is surrounded by two membranes that compartmentalize DNA from other cellular components. The term membrane refers to a thin, double-layered film of fatty molecules called lipids, so the double membrane surrounding the nucleus consists of two such lipid films. Membrane-bound compartments in the cell separate different sets of molecules and biochemical reactions from each other. Numerous nonmembrane-bound organelles also populate the cytoplasm of eukaryotic cells. Prokaryotes and eukaryotes have a few nonmembrane-bound organelles in common, but most organelles are strictly eukaryotic (fig. 1.4).
How important is normal organelle function for human health? The answer comes from a brief look at what membrane-bound organelles like the nucleus, mitochondrion, and lysosome and nonmembrane-bound organelles like microtubules, microfilaments, and ribosomes (fig. 1.4) do for the eukaryotic cell and what happens when they fail.
The mitochondrion is the "powerhouse" of the cell because it is where energy-rich food molecules are burned (oxidized). Energy released by oxidizing food is used to produce ATP, the common energy currency for the cell. Just as the euro is the common monetary currency for European Alliance countries, ATP is the one energy-rich molecule recognized and used by all parts of the cell to maintain life's activities. Without ATP, cells die. ATP fuels cell movement, reproduction, sensory perception, and even our thoughts. Like the nucleus, mitochondria have two membranes surrounding them. Inside the mitochondrion's inner chamber and within the inner membrane itself, energy-rich molecules oxidize to form ATP (fig. 1.5). A typical cell contains several hundred mitochondria, and a human egg cell contains thousands.
Mitochondria are distinctive in two other ways: they possess their own DNA, and they are inherited from mothers. The maternal inheritance of mitochondria reflects their abundance in egg cells and absence in the portion of sperm cells that enters the egg at fertilization. By analyzing genes in mitochondrial DNA, biologists gain information about the maternal ancestry of organisms. Examining human mitochondrial DNA from indigenous populations worldwide led to the conclusion that all humans descended from one woman or a small group of women who lived in Africa about 250,000 years ago.
Several pathologies and diseases are associated with abnormal mitochondria. Ischemia from strokes and myocardial infarctions causes a rapid loss of mitochondrial function and cell death in the O2-depleted tissues. mitochondria in liver cells of alcoholics fuse with each other to produce dysfunctional megamitochondria. Conditions associated with mitochondrial DNA mutations or damage include blindness, deafness, seizures, infertility, muscle tremors characteristic of advanced Parkinson's disease, and premature aging.
Lysosomes are small membrane-bound vesicles that serve as the cell's digestive sys tem. Inside lysosomes are powerful enzymes that break down large, ingested food molecules into smaller molecules that are eventually oxidized inside mitochondria or used to construct other components of the cell. Lysosomes also digest worn-out organelles, recycling the breakdown products for new building projects inside the cell. Sometimes lysosomes go berserk, digesting the entire cell from the inside out. This happens in the lungs of persons afflicted with asbestosis, a disease caused by asbestos fibers entering lung cells. Inherited diseases called lysosomal storage disorders result from genetic defects in lysosomes, rendering them unable to digest certain materials. The results are an abnormal accumulation of undigested material inside the cell and devastating diseases, including Tay-sachs disease, that cause mental retardation and joint and skeletal deformities. fortunately, all known lysosomal storage disorders can now be diagnosed prenatally by amniocentesis, so their occurrence is declining.
Microtubules are components of the cell's cytoskeleton, a complex array of tubules and filaments that serve as the "bones" and "muscles" of cells. They provide support and also direct cell movement, including the movement of objects inside cells. Microtubules are thin, hollow tubes that form a cytoplasmic scaffolding that maintains cell shape and orchestrates movements like the beating of sperm tails and the separation of duplicated chromosomes before cell division. In the lungs, thousands of microtubulecontaining, hair-like structures called cilia cover the surface of cells lining air sacs and passageways. Cilia beat constantly to provide a cleansing flow of mucus up and out of the lungs. Components of cigarette smoke poison ciliary microtubules; the cilia stop beating; nasty particles and other inhaled impurities build up in the lungs causing emphysema and cancer. Mutations in the genes for certain microtubule-associated proteins impair microtubule action inside sperm tails and lung cells causing infertility and emphysema.
Excerpted from Brutes or Angels by James T. Bradley. Copyright © 2013 by The University of Alabama Press. Excerpted by permission of THE UNIVERSITY OF ALABAMA PRESS.
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