Brutes or Angels: Human Possibility in the Age of Biotechnology

Brutes or Angels

HUMAN POSSIBILITY IN THE AGE OF BIOTECHNOLOGY

JAMES T. BRADLEY

THE UNIVERSITY OF ALABAMA PRESS

Tuscaloosa

Copyright © 2013

The University of Alabama Press

Tuscaloosa, Alabama 35487-0380

All rights reserved

Manufactured in the United states of America

Typeface: Perpetua and Helvetica

Cover art: man x-ray, ©iStockphoto.com/cosmin4000;

Genetic Rain, ©Istockphoto.com/mstay.

Cover design: Erin Bradley Dangar / Dangar Design

∞

The paper on which this book is printed meets the minimum requirements of American national standard for information sciences—Permanence of Paper for Printed Library Materials, ANSI Z39.48-1984.

Library of Congress Cataloging-in-Publication Data

Bradley, James T., 1948–

Brutes or angels: human possibility in the age of biotechnology / James T. Bradley.

pages cm

Includes bibliographical references and index.

ISBN 978-0-8173-1788-1 (trade cloth: alk. paper)—

ISBN (invalid) 978-0-8173-8658-0 (ebook)

1. Genetic engineering—Moral and ethical aspects. 2. Human Genome Project—Moral and ethical aspects. I. Title.

QH442.B72 2013

174.2—dc23

2012035096

For my grandchildren and their descendents

Contents

List of Illustrations

Preface

Acknowledgments

Introduction

1. Cells and Molecules: The Unity of Life

2. Stem Cells: Embryos, Therapeutic Cloning, and Personhood

3. Embryo selection: Preimplantation Genetic Diagnosis

4. The Human Genome Project: spin-Offs and Fallout

5. Human Diversity, Genes, and Medicine: Richness and Dangers

6. Genetic Enhancement: Humankind Healing and Redesigning Itself

7. Human Reproductive Cloning: sameness, Uniqueness, and Personal Identity

8. Age Retardation: Chasing Immortality for Better or Worse

9. The Mind: Neuroenhancement and Neuroethics

10. Synthetic Biology: From Cocreator to Creator

Conclusion

Epilogue

Glossary

References

Index

Illustrations

FIGURES

1.1. The three kingdoms of life

1.2. Water and glucose molecules diagramed

1.3. Cell structure seen by light microscopy (LM) and transmission electron microscopy (TEM)

1.4. Prokaryotic and eukaryotic cell structure

1.5. Mitochondrion structure and function

1.6. Three-dimensional protein structure

1.7. The central dogma of biology

1.8. Relationships between DNA, genes, and chromosomes

1.9. Life cycle of humans and other sexually reproducing organisms

1.10. Comparison of mitosis and meiosis

1.11. The endosymbiotic origin of mitochondria

2.1. Generalized stem cell biology

2.2. Blastocyst-stage embryo characteristic of humans and other mammals

2.3. Assisted reproduction by in vitro fertilization

2.4. Creation of an embryonic stem cell (ESC) line

2.5. Normal developmental potential of a hemopoietic stem cell

2.6. Derivation of pluripotent, human embryonic germ cells

2.7. Induced pluripotent stem (iPs) cells

2.8. Therapeutic and reproductive cloning

2.9. Stages of early embryonic development in humans and other mammals

3.1. Preimplantation genetic diagnosis by single-cell biopsy

3.2. Single-cell biopsy from a three-day-old human embryo

3.3. Creation of a savior sibling to provide hemopoietic stem cells

4.1. The epigenome consists of chemical modifications

4.2. Higher primate ancestral tree

5.1. Diagrammatic representation of how single nucleotide polymorphisms and genes with disease-causing mutations are inherited together

5.2. Summary of early modern human migrations from the site of our species’ origin in East Africa

6.1 Michelangelos's David

6.2. Somatic cell gene therapy

6.3. Germ-line gene therapy via genetically engineered eggs

7.1. Dolly, the cloned sheep, and her lamb, Bonnie

7.2. Enucleation (removal of the nucleus) procedure for a mammalian egg

7.3. Cloning by somatic cell nuclear transfer

9.1. A neuron with its three major parts: cell body, axon, and dendrites

9.2. The adult human brain with its three major parts: cerebrum, cerebellum, and brain stem

9.3. A chemical synapse

9.4. Removal of neurotransmitter from the synaptic cleft

9.5. Neuroenhancer action at chemical synapses

10.1. The interdisciplinary nature of synthetic biology

10.2. Top-down synthetic biology uses genes or other components of existing organisms to generate radically new forms of life

10.3. Bottom-up synthetic biology aims to build living cells from scratch

10.4. Creation of a minimal genome from the natural genome of a living microbe

10.5. Transformation of one species into another by genome (DNA) transplantation

TABLES

2.1. Biological signposts during human development

3.1. Some genetic diseases and conditions diagnosed by PGD

6.1. Types of human genetic engineering

6.2. Types of eugenics

Preface

It should be the aim of every scientist to eventually generalize his [her] views of nature so that they make a contribution to the philosophy of science.

—Ernst Mayr, This Is Biology: The Science of the Living World

The objective of this book is to facilitate informed choice making about personal use of biotechnologies and formulation of public policies governing their development and applications. The book provides basic information about a wide range of biotechnologies, the ethical issues raised by each one, and diverse viewpoints on dealing with these issues. Two underlying premises imbue the book:

1. Earth's life forms are products of nature and share a common ancestry extending back about 3.8 billion years.

2. Life's processes are coming increasingly under human control. Appreciating how life got to where it is today can foster wisdom in choosing its future directions.

No formal learning in biology is needed to read and understand this book. In chapter 1 the basic principles of cell and molecular biology are laid out for readers wishing to begin with scientific fundamentals underlying the biotechnologies described in succeeding chapters. Chapter 1 tells how molecules and cells are organized into living things and why it matters to know something about how cells work. Chapter 1 aids and enriches understanding of later material, but some readers may choose to begin with a later chapter, exploring straightaway a specific biotechnology with its ethical, legal, and societal implications: stem cell research and therapy, embryo selection, the Human Genome Project and human genomics, genetic enhancement, cloning, age retardation, cognitive enhancements, or synthetic biology. Chapters need not be read chronologically.

Chapters 2–9 address biotechnologies that directly involve human beings at the levels of developing embryos, cells, genes, and brain function. For example, chapter 5, on human genomics, includes special sections on genes and ethnicity that explore the benefits and risks of using genomic information about human diversity to advance health care and disease prevention. Chapter 10 examines the burgeoning field of synthetic biology and our emerging role as creators of life itself. Each chapter has two objectives:

1. to present the science required for making informed choices about developing and using a particular biotechnology and

2. to encourage personal reflection on human values as they relate to the biotechnology.

Metaphors, analogies, drawings, and photographs help convey information about important biological principles and biotechnological procedures. I strive to present multiple views on the ethical issues without bias. However, when a particular viewpoint is based on the misuse or misunderstanding of scientific information, I point that out.

The theme of the book is that the interface between modern biotechnologies and human values is very dynamic, changing as biotechnologies develop and as individual human minds and entire societies respond to their understanding of those biotechnologies. Different technologies raise different ethical issues. For example, defining personhood is the major issue facing use of human embryos for embryonic stem cell research; the meaning of personal identity arises with reproductive cloning; privacy and ethnic discrimination are issues for human genomics; the meaning of human authenticity and human nature crop up with neuroenhancement and genetic enhancement; eugenic issues arise with preimplantation genetic diagnosis; the biological and societal significance of death occurs with age retardation; and appropriate actions and responsibilities for creators of new life forms accompany synthetic biology.

All twenty-first-century biotechnologies bring up the issue of distributive justice. Who will benefit most from these technologies, and will the benefits be accessible to people who need them the most? How should finite public funds and research time be used? Discussion of these and related questions of distributive justice occur throughout the book. Some writers prefer to use the term moral when referring to religion-based codes for behavior and ethical for secular-based guidelines. I do not make this distinction but instead use the two terms interchangeably, as do most bioethicists.

At the end of each chapter is a set of questions for thought and discussion suited for personal reflection and group dialogues. Most of the questions have no single, correct answer; rather, the questions are important for the public discussion needed to shape wise policies at state, national, and international levels.

A comprehensive glossary follows the epilogue. Although nontechnical language is used throughout the book, certain terms like molecule, protein, DNA, gene, blastocyst, germ cell, and zygote are needed for clarity and accuracy when discussing a particular biotechnology and the ethical issues arising from it. Each such term is italicized and clearly defined when it first appears in the text. Then, when it first appears in a later chapter, it is italicized again to signal that its definition appears in the glossary. Notes and sources for additional information are included for each chapter, and a comprehensive reference list and detailed index complete the book.

Acknowledgments

Many persons contributed ideas and tangible support for this project. Sue Bradley, Isabelle Thompson, and Amy (Gordon) Jones read and edited major portions of the book before the manuscript was submitted for publication. Christine Probst, Alondra Oubre, Lana Saffert, and the late Martha King read chapters on cloning, the genomics of human diversity, neuroscience, and stem cells, respectively, and gave valuable advice for improving them. I am also grateful for numerous and regular conversations about biotechnology and bioethics with many persons over many years. These conversations helped me to see what things were most important to write about and how best to write about them. Insights and questions from my wife, sue Bradley, were invaluable in this department. Others contributing time and illuminating conversation include, but are not limited to, Ray Allar; my mother, Marge Bradley Scholl, and late father, Donald L. Bradley; my daughters, Laura Bodt and Sara Compaglia; John Bodt; my sister, Marilynn Bradley; John Compaglia; Gerry Elfstrom; Keith Gibson; Franco Giorgi; Robert Greenleaf; Peter Harzem; Katie Jackson; Jay Lamar; Clark Lundell; Anthony Moss; Gary Mullen; Leonard Ortmann; Randy Pipes; Teresa Rodriguez; Michelle Sidler; Michel Smith; Timothy Terrell; Frank Werner; the sisters in P.E.O. International, chapter E, Auburn, Alabama; the leaders and participants in the 2003 Intensive Bioethics Course XXIX at the Kennedy Institute of Ethics at Georgetown University; my genethics course students at Auburn University; and Tim Turner's research ethics students at Tuskegee University. I am grateful to the science and mathematics teachers who inspired and nurtured my interest in those ways of knowing, from junior and senior high school in Rice Lake, Wisconsin (George Theis, James Stauffer, Thomas Ritzinger, Karl Schmid, and Wayne Arntson), through my education at the University of Wisconsin (notably, C. H. Sorum and James F. Crow). And I owe unique debts of gratitude to my major professor at the University of Washington, the late John Edwards, for demonstrating the value and fun of expanding one's creative endeavors beyond a single, narrow scientific niche; to molecular biologist and bioethicist Kevin Fitzgerald at Georgetown University for advising me that a cell biologist can contribute to the discipline of bioethics by simply doing it; and to the late evolutionary biologist, science historian, and author Ernst Mayr (1904–2005) at Harvard University for challenging and encouraging me to write for a general audience about the philosophical significance of cell biology.

I am fortunate to have Janna Sidwell as my primary illustrator. Her patience with me, professionalism, dedication to the project, and artistic talent are largely responsible for making the biological concepts accessible to non-biologists. Sara Agnew also contributed to some illustrations, and undergraduate Erin Beebe helped research many topics. I thank my department chairs, James Barbaree and Jack Feminella, and my dean, Stew Schneller, at Auburn University for encouraging my foray into bioethics and book writing. I also thank Elizabeth Motherwell, senior acquisitions editor for Natural History and the Environment at the University of Alabama Press, and freelance editor Karen Johnson and project editor Jon Berry for the many ways they supported this project—with encouragement, work, and wisdom. The constructive critiques of three anonymous reviewers were also invaluable. Finally, my deepest gratitude goes to my wife, Jackie sue, for her constant encouragement and patience with my geographical absences and mental distraction while writing.

Introduction

Who is there that does not wonder at man? . . . [M]an fashions, fabricates, transforms himself into the shape of all flesh, into the character of every creature.

—Giovanni Pico della Mirandola, Oration on the Dignity of Man

Humankind's place in nature is somewhere between brutes and divinities according to Renaissance philosopher Pico della Mirandola (1463–1494). Writing what some consider to be the manifesto of the Renaissance, Pico allegorized humankind's creative potential. He imagined God telling humans how they differ from other creatures:

The nature of all other beings is limited and constrained within the bounds of laws prescribed by Us. Thou, constrained by no limits, in accordance with thine own free will, in whose hand We have placed thee, shalt ordain for thyself the limits of thy nature . . . with freedom of choice and with honor, as though the maker and molder of thyself, thou mayest fashion thyself in whatever shape thou shalt prefer. Thou shalt have the power to degenerate into the lower forms of life, which are brutish. Thou shalt have the power, out of thy soul's judgment, to be reborn into the higher forms, which are divine. (Pico della Mirandola [1486] 2005, 287)

Pico prepared his famous Oration as the opening statement for a debate in Rome during the winter of 1486–1487, but since some of Pico's theses were ruled heretical, the debate never occurred.

Pico's fifteenth-century words are remarkable in that they describe with uncanny accuracy our twenty-first-century understanding of humankind's position in nature. Modern paleoanthropology and molecular biology tell us that Homo sapiens evolved some two hundred thousand years ago from brutish bipedal ancestors who climbed, walked, and ran in Africa nearly five million years ago. And evolutionary psychologists do little better than Pico in describing how humans differ from other animals: humans philosophize and theologize about how best to live their lives, while other animals probably do not. With the biotechnologies described in this book, humankind is poised to shape its biological future very nearly as Pico mused over five centuries ago, for better or worse, according to how we exercise our judgment.

Humankind is in an age of biotechnology. Our relationship with biotechnology during the next decade or so will largely determine the future nature of our species and the rest of the living world. Homo sapiens’ future, whether we degenerate or are reborn into higher forms, will reflect the thoughtfulness we bring to decisions about how to use twenty-first-century biotechnologies.

The inspiration for this book came in an e-mail message from my lifelong friend Ray. It was 1999. Completion of the base sequencing of DNA for one of the twenty-three human chromosomes had just been announced by news media. Hey, what the hell does this mean, ‘sequencing a chromosome,’ and why should I care? wrote Ray. I began a reply that included a description of DNA molecules and how they carry hereditary information for both desirable traits and genetic diseases. But, after spending thirty minutes on an abbreviated answer to his very good question, I wrote, "Ray, you ask a great question, but there's more to the answer than this. So I'm going to write a book for you about cells, genes, DNA, and the new biotechnologies. I hope you will find it interesting. Within minutes Ray's short reply appeared on my monitor: Thanks, Jim, I just hope you finish it before I forget my question." The book project took longer than expected, so I've periodically reminded Ray of his initial question and, in the meantime, answered a few others.

While writing, I had not only Ray in mind, but also my musician wife, nonscientist parents, sister, daughters, friends, and students. Their questions about stem cells, cloning, genetic engineering, in vitro fertilization (IVF), and other biotechnological terms in the news helped me identify the book's topics.

I began this introduction with Pico, from the small village of Mirandola in northern Italy, who imagined humans between animals and divinities, with the ability and authority to develop in either direction. A twentieth-century thinker just as creative and inquisitive as Pico was Jacob Bronowski (1908–1974), who began his classic book, The Ascent of Man, with a chapter titled Lower than the Angels. Here is his description of our species: Man is a singular creature. He has a set of gifts which make him unique among the animals: so that, unlike them, he is not a figure in the landscape—he is a shaper of the landscape (Bronowski 1973, 19).

What Bronowski did not foresee in 1973 is that in addition to shaping our environment, we would soon become sculptors of human nature itself. So here we are, early in the twenty-first-century, between brutes and angels, with burgeoning abilities to enhance, engineer, manipulate, and even create life in ways unimaginable just a few decades ago. Deciding how to develop and use these powers will not be easy, but we must do it.

Living a good life in the Age of Biotechnology requires gathering reliable information, listening carefully and respectfully to others’ views, formulating one's own views thoughtfully and deliberately, and maintaining open pathways for dialogue. It also requires being open to changing one's views in light of new information, either in the realm of science or in the area of ethical argumentation. As humankind moves into the Age of Biotechnology, I am hopeful for its future in proportion to the diligence with which we exercise our skills in gathering information, conversing with mutual respect, being open to change, and formulating thoughtful opinions.

1

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 system and the germ theory for disease.¹ 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 manmade 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 CgH12Og. 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.² 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.³

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.⁴ 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.⁵

Lysosomes are small membrane-bound vesicles that serve as the cell's digestive system. 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.⁶ 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