Sex and the Origins of Death

Kirkus Reviews, September 15, 1996. (Staff reviewer)
"We die because our cells die," Clark says. Death is "the evolutionary consequence of the way we reproduce ourselves." The sole function of cells, human or otherwise, is to replicate their DNA; once finished, they are programmed to die. That is, once a job is done, such as growing fingers out of web-like structures in human embryos, certain cells have no further task and die. "Programmed" is a key word here: In a number of clever laboratory experiments, healthy cells reproduce themselves only to a point, and undergo a process of exploding outward, called apoptosis. If the process is blocked, cells have a tendency to become cancerous and, at the least, will stop dividing. Only cancer cells and certain ancient single-cell life forms are, in a manner of speaking, immortal, but they, too, will eventually die by overcrowding or when they run out of food. Clark proceeds to discuss how the nature of cell death relates to the agonizing debate over a patients "right to die," detailing the strange findings at Karen Ann Quinlan's autopsy and relating it to yet another incidence of near death: the spores by certain animal forms in times when nature makes it hard to reproduce. The minuscule spores of briny shrimp truly seem to be dead but, when chilled to absolute zero and placed in a correct environment, will begin to cycle again. Clark ends by speculating about so-called "nonsense DNA." Is it a useless relic of the evolutionary process, or does it hold the keys to an explanation of why we are here in the first place? His discussion of biology flows into a discussion of metaphysics. Strikingly well argued and clear.

Amazon.com
Despite its provocative title, Sex & the Origins of Death is not as sensationalistic as it sounds. William R. Clark is a professor of immunology at UCLA, and his avowed intention is to enlighten his readers rather than to frighten or titillate. Drawing on his broad knowledge of the cellular systems that make up our bodies and the medical and ethical arguments on the nature of death, he presents a compelling tale of the evolution of sex and death interwoven with a story of a man experiencing a heart attack. This juxtaposition humanizes the discussion and grounds the reader firmly in day-to-day reality, even when considering such bizarre topics as immortal bacteria and Sea Monkey spores.

Clark covers the development of sex in microorganisms and how this novelty may have guaranteed the inevitability of death (though perhaps not that of taxes). From this level of thinking, he changes quickly to 20th-century American law, which has pondered the question of death at great length as our scientific prowess has enabled us to maintain deeply traumatized individuals in persistent vegetative states, presumably free from conscious awareness of any kind. Now that death has become a matter of opinion, Clark insists that we pay careful attention to it, both as scientists and as human beings. Sex & the Origins of Death is a great place to start. --Rob Lightner

From Booklist , November 1, 1996
Billions of years ago, single cells lived, died, and disintegrated. As cells grew larger and multicellular creatures evolved, sexual reproduction entered the picture, and somatic (body) cells had to protect the DNA in the germ cells until it could duplicate itself and continue to exist, at which point the particular somatic cells were no longer needed. Clark points out that there are two basic types of death, one caused by accident or necrosis, and the other caused by suicide or programmed cell death. The latter, apoptosis, was discovered and named just 24 years ago, and much of the information Clark draws on has been more recently discovered. Nature sees no difference between the deaths of brain, liver, or foot cells, but human beings evaluate their minds and bodies in a less impartial manner. Accordingly, Clark explores some of the social, philosophical, and religious aspects of human beings in his lucid, thought-provoking work that concludes that, in the long view, humans differ not at all from other living creatures. William Beatty
Copyright© 1996, American Library Association. All rights reserved

The American Scientist, September/October, 1997. Reviewed by Thomas W. Traut.
As young people are frequently warned, sex can have bad consequences. This book presents the ultimate form of this message: Because of sex, we must all die. In a culture as obsessed with sex and death (or its avoidance) as we are, the somewhat whimsical title is an obvious eye-catcher.

In this very comprehensible book, William Clark uses a lively and engaging style to develop an interesting hypothesis. An experienced cell biologist, Clark inserts a fictitious cardiac arrest story that he develops in alternate chapters to illustrate some of his concepts. Obviously all cells and organisms can die as a result of physical trauma or chemical poisoning, but we now also know that most cells, whether as individual organisms or as parts of multicellular organisms, are genetically programmed to die. The biochemical mechanisms and sequence of events leading to programmed cell death - apoptosis - have been defined in the past 15 years. In some situations we see this as logical or clever, since it is necessary for the development of the embryo. It is, for example, by programmed death of connecting cells that the fingers of the hand achieve their independence from the adjacent digits, so that we do not maintain the webbed hand shape initially formed in the fetus.

But it is still not clear why all the body's cells must die. Clark nicely explains the evolutionary origin of programmed death in simple, single-cell Paramecia. Since all cells, even Paramecia, suffer mutations to their DNA, their survival clearly depends on the ability to monitor and repair such damage constantly. However, because such repair systems are never 100 percent effective, damage accumulates. The discovery of sex, and conjugation of individual Paramecia cells to exchange DNA, was an evolutionary improvement to DNA repair systems. Although such exchange might transfer damaged DNA, it could also transfer good DNA to a cell that might otherwise be in trouble. For the new DNA to be useful, the old DNA that was being replaced had to be removed. Thus the earliest example of programmed cell death was for macronuclei, containing the Paramecium's DNA.

Clark also describes various examples of natural efforts to avoid death. Bacteria form spores in times of environmental stress by developing a special protective coat, removing almost all the intracellular water and halting biochemical processes. Such spores can exist for many years even under extreme conditions of cold and pressure, until they encounter a more favorable environment and convert back to living cells. Viruses, which are not truly "alive," also have no internal water or metabolism, carrying out all their metabolic functions only after invading a living cell. Examples of such cryptobiosis are found even in invertebrates such as brine shrimp embryos. This is not suggested as a possible option for mammals, even though there is interest in the freezing and extended storage of people after death in anticipation of a reawakening in a future era of death-reversing technology.

In addition to a quite comprehensible presentation of the underlying cell biology and evolutionary changes, Clark also delves into the philosophy and ethics of euthanasia. Returning to his narrative of a cardiac patient, Clark explores the ethical options available to family and physicians as the patient remains in a coma. This chapter contains little science, but the religious/moral challenge of euthanasia is quite relevant.

New Scientist, December 14, 1996. Reviewed by Thomas Kirkwood.
Anyone who reckons that science writing is dry stuff may find their outlook broadened by this little book about the biology of death. We join William Clark aboard a myocardial cell deep inside the heart of a man undergoing his second, and ultimately fatal, heart attack. The narrative is gripping as the cell itself nears the point of death: "Partially finished products of every description begin to fall off the assembly lines as ATP-dependent enzymes wait for new energy supplies to arrive. Chaperones of the unfit and incomplete rush to transport them to disposal units. The lysosomes are driven to a frenzy as they try to deal with all the trash being fed into them. Everywhere the cry is the same: 'Where is the ATP?' But the ATP never comes…"

…Sex and the Origins of Death deals with two basic themes: death and senescence. Sex comes into the story only in relation to the origins of senescence. Broadly speaking, death comes in two forms, that which is meant to happen, and that which is not. At the cell level, this is manifest as death either by apoptosis or necrosis. Apoptosis, also known as programmed cell death, or cell suicide, is a tidy death. Neighboring cells neatly dispose of the corpse.

Clark takes us aboard a cell that is dying this way. Its death will help to form a gap between the fingers of a developing baby. Necrosis, by contrast, is a messy death. Cell debris lingers and can trigger an inflammatory response. The dying myocardial cell died by necrosis; its death was not meant to happen.

This brings us to the thorny problem of senescence. Is it meant to happen or not? Clark links the origin of senescence with the evolutionary emergence of a distinction between the germline and the soma. The germline comprises the reproductive lineage through which genes are transmitted and this must, in a sense, be immortal. We are products of a germline that extends to the beginnings of life on earth. The germline in humans is transmitted through sperm and egg. The soma is the rest of the organism and does not contribute genetic material to the offspring. It is mortal.

…In the wider context, Clark explores the boundary between life and death in interesting ways. His heart attack victim is resuscitated but does not regain consciousness and enters a persistent vegetative state. Is this life or death? There can be no doubt that looking at death in the right way can tell us a lot about life.

Nature, 19 December, 1996. Reviewed by Harriet Coles
Some organisms can survive extreme conditions in a state of suspended life - or reversible death - called cryptobiosis. Encysted embryos of the brine shrimp Artemia salina kept only 2.2^o above absolute zero for six days hatch as successfully as those kept at room temperature.

The nineteenth century scientists who saw cryptobiosis as a possible biological basis for resurrection are forgiven for being "sophomoric." …This is a precautionary measure by the author, who asks, in the light of late-twentieth century evolutionary and cell biology, "what is death?"

Death is variously defined by Clark as the destruction of a genome, the loss of whole-brain function, the end-point of senescence, the genetically encoded self-destruction of cells (known as apoptosis), the end of 'self' and…what happens to a mouse when an elephant sits on it.

In exploring each of these forms of death, Clark moves seamlessly from the rare Hutchison-Gilford syndrome in which 13-year-old children die of old age, to the p53 gene as a master switch between the life and death of a cell, and the ethical dilemma of maintaining more and more people in a persistent vegetative state.

The "sex" in the title of the book is more than just a marketing ploy. Clark translates the age-old conceit of sex and death (which can be traced from the poetry of John Donne to Hollywood screenplays by way of Freud) into the language of evolutionary biology. One of the earliest sexual reproducers to evolve - the single-celled organism Paramecium - also evolved the programmed destruction of DNA used for cell maintenance, but not of DNA set aside for reproduction. Seen from this perspective, multicellular organisms are an elaboration of this theme of division of labor into somatic and germline DNA. Clark eloquently traces the ancestral roots of both programmed cell death and, more indirectly, death of the whole organism to the evolution of sex in paramecia.

At best, this book is an enjoyable and eminently readable collection of light essays on the several definitions of death and life, but it aspires to be much more. It is the second popular book in two years by Clark, and in it he goes where the most respected investigators of apoptosis and senescence fear to tread. He tries to arrange this smorgasbord of deaths around such seemingly profound statements about life as "Death is not inextricably intertwined with the definition of life," "…in multicellular organisms death always begins with the death of single cells," and "If life is the interaction of structure with energy, then it follows that death at the level of a single cell must represent either the loss of structure or of energy." However dazzling I found these brain-teasers, it was disappointing to realize I had been made giddy by nothing other than my own all-too-human desire for ultimate answers.