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CHAPTER 1
Cells, Molecules, Genes, and Nature
A cell is regarded as the true biological atom.
— George Henry Lewes, The Physiology of Common Life (1860), 297
Twenty-first-century humans live at a remarkable time in the history of the 13.8 billion-year-old universe. Earth coalesced from a gaseous cloud of elements and other interstellar debris just 4.6 billion years ago, and living cells adorned the planet about 3.8 billion years ago. Homo sapiens is a mere 200,000 years old. If the length of one's entire arm represents the time life has ranged over the Earth, all of recorded human history is as airborne fingernail dust from a single swipe of a nail file. Our species is very young compared to many others. For example, dinosaurs ranged the planet for 135 million years. What is remarkable about being alive now is that during our moment in time, the universe is coming to understand itself, perhaps for the first time. What I mean by that becomes clear through the first of the following questions this chapter addresses:
1. Why can we state that humans are literally star dust?
2. What are atoms, molecules, cells, and genes?
3. What is the relationship between DNA and protein, and why does it matter?
4. What is a genome?
5. Why is it important to think now about how humans will use biotechnologies many generations hence?
6. What should every school girl and boy know about life on Earth?
7. How does research with cells and genes intersect with human values?
Life, Nature, and Their Future
In this section, we examine questions 1–5. We will gain some fundamental information about the matter of which we and other living things are composed. This information is valuable when we later consider biotechnologies including brain scanning, monitoring, and manipulation; genetically modified organisms; gene editing; artificially intelligent robots; and more. Hopefully, we will also acquire a viewpoint about life that aids in making decisions about how best to develop and use powerful biotechnologies. We begin with our very beginning, the origin of the atoms in our bodies.
Humans Are Star Dust
It is a fact that we are literally star dust. Atoms comprising the cells of all living things were forged inside one or more stars more massive than the sun. The smallest and most plentiful atoms in the universe are hydrogen (H) and helium (He). They comprise the bulk of burning stars. Stars are gigantic fusion reactors in which gravity forces H atoms together to form He, releasing huge amounts of atomic fusion energy in the process. The most powerful nuclear weapons are atomic fusion bombs in which H nuclei fuse to produce He, just as happens inside the sun. Energy emanating from the sun is directly or indirectly responsible for all of life's activities, our weather patterns, and geological phenomena such as weathering and erosion. Sunshine powers the water cycle: precipitation, evaporation of surface water to form clouds, condensation, and back to precipitation. This water cycle formed the Grand Canyon, the Badlands of South Dakota, and Niagara Falls.
But what about us and star dust? When the H fuel of a star runs low, the outward radiation of energy and matter is insufficient to fully counter the inward collapse of the star due to gravity. The collapsing star creates unimaginably enormous forces in the star's interior, resulting in a cascade of atomic nuclear fusions that creates all 115 known elements in the chemist's periodic table. Finally, the huge imploding star explodes as a super nova and spews its forged elements into space as a vast cloud of star dust from which planets ultimately coalesce. Life arose on at least one such planet about four billion years ago. Perhaps it has on others as well.
Some of that star dust from an ancient super nova is self-conscious, learning about its origin and about the chemistry that made it conscious. We are truly star dust, and our particular configuration of star dust realizes this fact. This self-conscious bit of the universe now has the technological acumen to take charge of its own future evolution and perhaps even to entertain itself by animating inanimate star dust and designing entirely new beings in the visage of synthetic organisms and autonomous, thinking robots. That is a remarkable thing. We are the universe contemplating itself and recreating nature.
What does this cosmic conversation have to do with the subject of this book, biotechnologies and their ethical and societal implications? It puts contentious issues into perspective by emphasizing our cosmic commonality. The fact that we each are bits of the universe attempting to understand ourselves and each other, our place in nature, and the larger whole of which we are integral parts can be an equalizer and a unifier. I believe that this knowledge nurtures respect, tolerance, and empathy between us and for the rest of nature, and virtues like these can facilitate wise decision making about developing and using technologies able to reform human nature and nature itself.
Humans are sentient, reasoning, components of the universe with the capacity of foresight to gauge the long-term effects of their actions on other components of nature. Reason and foresight set us apart from the rest of the universe as we now know it and obligate us to protect our planet from potential harmful effects of some of the very technologies discussed here. In 1949, ecologist and conservationist Aldo Leopold argued that an action is right if it promotes the integrity, stability, and beauty of the land and that it is wrong if it does otherwise. The overarching mission of this book is to provide information about twenty-first-century technologies with transformative powers for both right and wrong, according to Leopold's definitions, and to show a path forward that promotes right action and minimizes wrong action.
This book is for persons with an urge to know, think, and converse about how modern technologies, primarily biotechnologies, are changing individual lives and society. Its reading requires no formal background in biology or chemistry. Only an elementary understanding of cells, molecules, and genes, which is provided by this chapter and at various other points along the way, is needed. Biotechnologies are technologies based on biology. They examine, manipulate, mimic, or redesign nature's biology so it befits us to know a bit about biology, the study of life from atoms on up.
Molecules, Cells, and Genes
Atoms comprise molecules and molecules comprise cells. Genes are portions of very large molecules called DNA, an acronym for its formal biochemical name deoxyribonucleic acid. Atoms like carbon (C), oxygen (O), hydrogen (H), nitrogen (N), sulfur (S), and phosphorus (P) comprise the molecules of living things. The most abundant molecule in living things is water (HO) whose formula indicates that one water molecule contains two atoms of H and one of O. Another small molecule, carbon dioxide (CO), is produced by animals as a by-product of metabolism and used by plants during photosynthesis. Plants growing hundreds of millions of years ago incorporated the carbon in CO into large molecules like cellulose that comprise plant tissues. When plants in ancient forests died and were covered with soil, they decayed and were compressed into coal and oil. Burning those large, primeval carbon-containing molecules as fossil fuels releases their C atoms into the air as CO, one of the greenhouse gases driving our current period of planetary warming. Other often-mentioned molecules of life include epinephrine, serotonin, dopamine, glucose, fructose, vitamins, amino acids, estrogen, and testosterone. Finally, all living things contain some very large classes of molecules referred to as the "big four": proteins, nucleic acids (DNA and RNA), lipids (e.g., cholesterol, saturated and unsaturated fats), and polysaccharides (e.g., cellulose and starch). We return shortly to two of these macromolecules of life, DNA and protein, but first consider some principles of cell biology.
Cells are the structural and functional units of all life on Earth, much as buildings are the building blocks of cities. As do buildings, cells come in many different types, more than two hundred in the human body. But unlike buildings, all cells come from preexisting cells. These two statements, that all living things are comprised of cells and that all cells are begotten by cells, constitute the cell theory. Observations recorded by three German scientists between 1838 and 1855 led to formalization of the cell theory and its elevation to a level of certainty enjoyed by other scientific theories such as the heliocentric theory for the solar system, the germ theory for disease, the atomic theory of matter, and the theory of evolution for biodiversity.
Known cells belong to one of three domains based on genetic analyses: Bacteria, Archaea, or Eukarya (fig. 1.1). Single-celled, microscopic organisms (microbes) comprise the Bacteria and Archaea. Eukarya too contains single-celled organisms like yeast and amoebae, but it also includes all multicelled plants, animals, and fungi. Bacteria is by far the most diverse of the three domains. In fact, a 2016 genetic study of microbes found in California meadows and deep sea vents turned up numerous new phyla belonging to a previously unknown evolutionary limb of the Bacteria domain (Hug et al. 2016). Bacteria's other limb also contains thousands of species including familiar beneficial and pathogenic microbes that live in our gut, on our skin, in our nostrils and other orifices, and in the soil. Bacteria give us infections and food poisoning, cause Lyme disease, and produce rotten apples. They also create yogurt and cheese, enrich the soil with nitrogen, and promote good health via our gut microbiome.
Archaea are Bacteria-like in appearance, small singled-celled microbes without the internal structures described below for Eukarya. Surprisingly, in the late 1970s, Archaea were discovered to be genetically more closely related to the Eukarya (which includes humans) than to the Bacteria (Fox et al. 1977), an evolutionary relationship confirmed many times over since then. Archaea live in extreme environments like the hot springs in Yellowstone National Park, high salinity spots like the Great Salt Lake, and places with high methane levels. Before Bacteria and Archaea were recognized as two distinct evolutionary groups of cells, all the bacteria-like cells and certain algae were lumped together under the name prokaryote.
The Eukarya domain includes organisms from amoebae and yeast to aardvarks and yellow jackets, from mushrooms and hyenas to maple trees and humans. Eukaryotic cells differ structurally from cells in the other two domains by partitioning their genetic aterial (DNA) away from the rest of the cell inside a membrane-bound nucleus. The word eukaryote derives from the Greek eu- (good, true) and karyon (nut or kernel). Thus, cells of eukaryotes possess a true nucleus, a kernel-like object near the center of the cell visible with a conventional light microscope and very prominent in cells viewed by electron microscopy (fig. 1.2). In chapter 2 we see how cloning and mitochondrial therapy involving three-parent babies make use of the fact that eukaryotic cells compartmentalize their DNA inside a nucleus.
In summary, atoms from a supernova comprise the molecules that comprise cells, which emerged on Earth four billion years ago. The chain of life remains unbroken since its beginning. Genes provide molecular continuity between generations of living things. What is a gene?
The term gene was introduced by Danish plant geneticist and physiologist, Wilhelm Johansen, in 1909. At the time, gene was coined in opposition to pangene, a term referring to invisible gemmules of hereditary particles in Charles Darwin's 1868 theory of pangenesis for heredity. Darwin did not know about genes or DNA, but he did note how particular traits moved from parents to offspring and on down the generations. To explain this, Darwin hypothesized that different cells and tissues in an organism produced their own tiny, specific, unseen particles of hereditary information that collected in the reproductive organs and eventually entered the developing embryo to direct tissue and organ formation. In 1865, Austrian monk Gregor Mendel reported experimental evidence for invisible "factors" of genetic information and laws governing their passage between generations, but his work was not appreciated or its significance understood until 1900, eighteen years after Darwin's death.
Working with the fruit fly Drosophila melanogaster between 1908 and 1915, American geneticist and evolutionary biologist Thomas Hunt Morgan gathered experimental evidence linking the concepts of Mendel's genetic "factors" and Johansen's genes with a recognition that hereditary factors reside in chromosomes visible with conventional light microscopes. From then through the 1940s, several biologists, including one of my biggest heroes, Harvard biologist Ernst Mayr (1904–2005), put evolutionary biology on a mathematical and genetic footing and established what came to be called the modern evolutionary or neo-Darwinian synthesis. Soon the genetics of entire populations of organisms were described mathematically, and the evolutionary roles of genetic diversity within and between populations became analyzable.
The discovery of DNA's chemical and geometric structure by Erwin Chargaff, Rosalind Franklin, James Watson, Francis Crick, and others in the early 1950s ushered in the present era of molecular biology and biotechnology. Pulitzer Prize–winning physician-scientist Siddhartha Mukgerjee (2016) wrote a magnificent natural history of the gene for the enjoyment of nonscientists, so I need not expand on the gene's history here. Mukgerjee guides readers from the sixth-century BCE ideas of Pythagoras that hereditary information is carried in semen through stepwise refinements of our understanding of heredity into our current era of genomics and burgeoning ability to edit virtually any gene in any organism on Earth.
So just what is a gene? In its natural form, a gene is a portion of a very long DNA molecule. In the cell, each of these long DNA molecules comprises one chromosome, and each chromosome contains hundreds to thousands of genes. Genes can be isolated from the context of their larger DNA molecules or simply synthesized in the laboratory without the additional DNA that normally surrounds them. In this case, the shorter segments of DNA are still called genes.
Most genes belong to one of two types: structural or regulatory. Structural genes contain information needed by the cell to produce other types of molecules, RNA, and/or proteins. Regulatory genes function to control the activity of other genes in the same cell. If a gene encodes some RNA or protein that in turn regulates the activity of other genes, we speak of that gene as a structural gene that codes for a regulatory gene product. Soon, we consider the protein products of genes further, but first we will briefly reflect on DNA itself.
All three domains of life encode genetic information within molecules of DNA. Some viruses encode their genetic information in a similar but different molecule called RNA, but biologists do not consider viruses to be alive, so here we focus just on genes made of DNA. Recall that a single molecule of DNA may contain many units of genetic information called genes.
DNA is a long, linear molecule comprised of four different structurally related subunits linked together. It is like stringing together beads of four different colors to make a chain thousands of beads long. If one assigned meaning (words or letters) to the sequence of bead colors, information could be encoded within and transmitted by such a chain of beads. It is the same for DNA molecules comprised of specific sequences of the four molecular subunits of DNA, abbreviated as A, T, G, and C. We need not concern ourselves with what these letters stand for or what their particular chemical structures are. It is enough to know that a gene consists of a particular sequence of these four subunits within a single strand of DNA and that the subunits are called bases. The length of the sequence of bases in a gene varies from fewer than one hundred to several thousand depending upon the gene's function. Most of the genes of interest to us here code for proteins. Appendix 1 describes how cells use information in DNA's base sequence to create proteins via the so-called central dogma of biology. Proteins are basic to life. In fact, virtually every structure in our cells, tissues, and organs and their proper functioning is directly or indirectly due to the properties of proteins. Knowing a few things about them will help us appreciate how genetic biotechnologies work.
Like DNA, proteins are large molecules comprised of a linear array of smaller subunits. The subunits of proteins are amino acids. The cell uses twenty different amino acids to build its thousands of different proteins. A single file of amino acids joined together creates a protein, and sometimes two protein chains wind around each other to create a multichained protein. Proteins bend and fold to acquire complicated three-dimensional shapes determined by interactions between the amino acids along their length (fig. 1.3). For example, if one amino acid is positively charged and another one negatively charged, they will be attracted to each other causing a bend in the region of the protein molecule lying between them. Similarly, two negatively charged amino acids repel each other causing a bend in the chain of amino acids, taking the two like-charged subunits further apart. Thus, the sequence of amino acids determines the three-dimensional shape of a protein, and the three-dimensional shape in turn gives each protein the properties crucial for its particular function in the cell.
(Continues…)
Excerpted from "Re-Creating Nature"
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