Steven M. Potter, March 11, 1986
(Written for Prof. Stanley Miller's Biochemical Evolution course)
Amongst the carbon compounds there is an abundance of evidence to prove the existence of internal tendencies or molecular properties which may and do lead to the evolution of more and more complex chemical compounds. And it is such synthetic processes, occurring amongst the molecules of colloidal and allied substances, which seem so often to engender or give 'origin' to a kind of matter possessing that subtle combination of properties to which we are accustomed to apply the epithet "living".
H. C. Bastian in The Beginnings of Life, 1872 (2)
The word "life" has probably been around ever since mankind began using language. It is a word of fundamental importance to all of us, and seldom do we make it through an entire day without putting it to use. We do so, however, with only a sketchy and subjective idea of what life actually means. This is because until recently, within the last century or so, it has been easy for people to distinguish between what they call living and what they call non-living. There has been no need to define life precisely; its meaning is intuitively understood.
The scientific revolution has brought complications into this matter: certain fields of science are concerned with systems which would be called living by some and non-living by others. For example, advances in medicine have brought about the discovery of microscopic "infectious agents" such as viruses and plasmids. Are these alive? Many scientists are presently searching for extra-terrestrial life. How will they know when they have found it, if life is not clearly defined? The recent advances in computer science portend that computers may eventually rival humans in their mental capacities. Can we ever call such man-made devices living?
Scores of researchers devote their time to the study of biochemical evolution to unravel the mystery of the origin of life on Earth. Though even the ancients concerned themselves with the origin of life, not until recently have theories in this area depended on chemical systems whose status as living or non- living is open to debate. Linus Pauling said (28) "In connection with the origin of life, I should like to say that it is sometimes easier to study a subject than to define it." Up to this point, scientists in this field have taken Pauling's "easier" route and avoided the issue of coming to a consensus on the definition of life. Two college texts, The Study of Life (27) and Life- An Introduction to Biology (32) were found to be lacking in a definition of "life". As the World Book Encyclopedia (18) put it: "Rather than trying to define life precisely, biologists concentrate on deepening their understanding of life by studying living things." How do they know what to study?
This paper serves to analyze the many different viewpoints on the meaning of the word "life". What does the scientific community consider "that subtle combination of properties" to be? It will not address the separate issue of the life of mankind, his purpose, etc. This will be left to the philosophers. It will also not include non-scientific, or "vitalist" (6) view on life. These propose forces specific to life which are not found in the realm of physics or chemistry. "Life" as it is used here is not to be confused with the lifetime of the individual.
This section presents what may be considered the classical properties of life, according to standard reference material. The 1984 Random House College Dictionary (30) defines life as: "The condition that distinguishes animals and plants from inorganic objects and dead organisms, being manifested by growth through metabolism, reproduction, and the power of adaptation to environment through changes originating internally." This latter property refers to the phenomenon of homeostasis, whereby an individual organism changes itself in response to a change in its surroundings. In other definitions (15,16,19) this is called "response to stimuli" or just "responsiveness".
Homeostasis is not to be confused with response of the species to environmental changes through the process of natural selection. This is evolution, and it comes about through the transmission of random mutations in the organism to its offspring. This ability to transmit mutations during reproduction, and thus be subject to the processes of natural selection, is a criterion of life cited by several references (12,16,21).
The Encyclopaedia Britanica (17) concentrates on metabolism in their biochemical definition of life: "An open system of linked organic reactions catalyzed at low temperatures by specific enzymes which are themselves products of the system." Some references include movement against a force (15,18) in addition to the other criteria. This may include locomotion or, in the case of most plants, growth against the force of gravity. The transfer of matter is another standard criterion listed (3,16). The consumption of raw materials and the excretion of waste materials are natural consequences of metabolism.
In general, life has traditionally been characterized in terms of growth, reproduction, metabolism, motion, and response (through homeostasis and evolution.)
The phrase "in terms of" was used in the last paragraph because each of the criteria mentioned are exhibited by different systems to varying degrees. The loopholes in such definitions are made evident by two sets of these systems: 1) Systems which we consider to be alive, but which don't exhibit all of the classical properties, and 2) Systems which we consider non-living, but which exhibit these properties.
The classic example from set 2 is fire. It grows, moves, metabolizes (consumes, transforms, and excretes matter,) reproduces, and responds to stimuli (e.g., wind). Crystals in a saturated solution will grow and reproduce more of their kind. The hydrosphere moves (in flowing rivers,) dissolves compounds and precipitates different ones out, reproduces from rain, and responds (by breaking a dam, say.) Such analogies have even been carried as far as free radicals, a species of individual molecules which reproduce, and can grow (into large polymers.)
The non-reproducing mule is an often-used example from set 1. It does not take part in the process of natural selection, yet few would deny that it is alive. Various seeds, spores, and even insects (9) can lay dormant for years without moving, growing, metabolizing, or reproducing, yet they are considered by most as part of what we call life. This dormant life is swept under a carpet called "cryptobiosis", meaning "hidden life".
There is a third category whose anomalous systems defy clas- sification into either set. One system in this category is the virus. On one hand, it is said (27) that "Viruses are not living organisms since they are incapable of independent existence." (They use the host cell's metabolic machinery in order to repro- duce.) On the other hand, it is argued (9) that "It sees unreasonable to deny that viruses are living just because they need help to do so." From the latter viewpoint, the virus is considered to be a parasite, a kind of microscopic leech.
Certain man-made systems are claimed to be forms of "protolife"(35), implying that they may have been the first forms of life on the earth. One category of these includes the coascervates and microspheres. These are produced by combinations of various immiscible liquids, for example: Sidney Fox's thermal proteins (produced abiotically) in water. These have been shown to form "cells" (droplets), to grow and move about, to bud and divide, and to aggregate. Their membranes exhibit selective permeability and even catalytic activity (10). Experiments have also been carried out with clay minerals. These spontaneously grow in layers. Various cations, when substituted into the silicate lattices of these clays, produce catalytically active sites. These active sites are "reproduced" in subsequent layers that form on the clays. Thus they "are capable of replicative self-multiplication," and are subject to the process of natural selection (35).
The systems mentioned in this section are proof that the classical definitions of life are not appropriate in many cases.
Many claim that there is a continuum of complexity, with simple inorganic systems at one end and the highest life forms at the other end (12,13,16,17,20). Systems which have been mentioned in the previous section lie somewhere in the middle of this continuum. It is believed that "There is no point along the continuum of existence from the simplest atom to the most complex animal, at which a line can be drawn separating life from nonlife." (17) Consider the electromagnetic spectrum as an analogy: at wavelength of 520nm, light is green; at 470nm, it is blue (8). But at what wavelength does it change from green to blue? There are an infinite number of blue-green shades in between the two extremes. The drawing of lines between green and blue, between living and non-living, is said to be arbitrary, a matter of personal preference."(13)
Others take the point of view that life is just an aspect of man's perception of matter, just as music is an aspect of his perception of sounds. It is purely subjective which sequences of sound will be perceived as music to an individual.
This sort of analysis has led Josephine Marquand to conclude that it is prudent to "avoid the use of the word 'life' or 'organism' in any discussion of borderline systems." (20)
One way to draw the line between life and non-life on the aforementioned "continuum of complexity" is to pick out a specific structural feature common to systems considered to be alive. The first such definition was that "all living systems are composed of cells."(5) In his study on the origin of life in the 1920's, A. I. Oparin postulated (13) that "only in discrete particles could the random chemical activity occurring in the waters of the earth be organized into harmoniously correlated chemical reactions." A corollary to this definition would be its converse: non-cellular systems are not living. We can not, however, deduce from this definition that all cellular systems are alive: the oil-vinegar emulsion in your salad dressing is composed of many cells, but is obviously on the non-life end of the continuum.
Another feature of "living systems" is the ubiquity of the linear polymers of amino acids we call proteins. These make up much of the structure and catalytic machinery associated with life on earth. Also ubiquitous are the polymers of nucleotides, the nucleic acids. DNA and RNA contain the genetic information which is passed on to the offspring of living organisms. Life has been defined (15) as that which makes use of or produces proteins and/or nucleic acids. More generally, living systems can be defined as those which exhibit optical activity and isotopic fractionation. The former refers to the rotation of polarized light by solutions of organic molecules. This is due to the chirality, or handed-ness, of these molecules. Often, when a molecule has two possible mirror images, a left one and a right one, only one of these forms is found in nature. For example, only left-handed amino acids are used in proteins and only right-handed sugars are stored for energy. Isotopic fractionation implies that life forms selectively pick out certain isotopes of the elements. This results in relative concentrations of these isotopes within them that differ from the relative concentrations in inorganic systems. (This provides the basis for carbon-14 dating.) These definitions are not foolproof; some inorganic and man-made systems also display these properties. Crystals of one handed-ness are produced routinely by chemists (22) and phase changes such as evaporation can result in isotopic fractionation.
If you grew up in Canada you might have been led to believe that only pine trees retain their foliage during the winter. If you then defined a pine tree as "a tree which stays green in the winter," you would run into trouble on coming to California, where trees which are not even conifers stay green all year. The definitions of life in this section may be of a similar nature. They are based on the particular mechanism by which life arose on earth, most likely a random process. Life may have arisen elsewhere (or earlier, here on earth) under different circumstances. It may then lack these structural features, yet still be considered life by other criteria, such as reproduction or metabolism.
Many definitions of life echo Leslie Orgel's belief (26) that "Living organisms are distinguished by their specified complexity." The terms order, information, and complexity are frequently encountered. How are these concepts related? Complex structures and systems abound in the universe, but most of them (the non-life, by this definition) are random, that is, they are not specified. We could define the "information content" of a structure as the minimum number of steps needed to specify the structure. To specify a random polypeptide (sequence of amino acids,) we need only state the proportions of the amino acids which go into making it. To specify a certain enzyme, however, we must state which acid occupies each position in the enzyme's sequence. This takes many more steps for an enzyme of the same length as the random polypeptide. Thus the enzyme has a higher information content.
"Order" has been defined (9) as "situations which are unlikely to occur by random processes." As the length of a specified protein goes up, the chance of producing that protein by hooking amino acids together randomly goes down exponentially. For a short protein of ten amino acids, for instance, there is a probability of about one in hundred trillion that it would be formed randomly. Since proteins in organisms are usually substantially longer than this, we can say that they are highly ordered.
Life has also been defined (7) not in terms of its order or information content, but in terms of its ability to transmit this information to its descendants, its ability to replicate. The human chromosome has about ten billion bits of information in it, and the half-set of these carried by a single sperm cell contains enough information to fill 500 large books (6). Certain viroids reproduce by transferring an RNA of less than 400 nucleotides to their host cell (34). While this is still a substantial amount of information, it is argued that these should not be considered living because they require not only the nutrients of their host, but also the information contained in the host cell's reproductive machinery. Francis Crick includes as a "basic requirement of life" (7) the ability of the system to replicate both its own instructions and any machinery needed to execute them.
Erwin Schroedinger, the famous physicist, analyzed life from a statistical perspective. He noted that in all inorganic systems, it takes a large, or statistical, number of molecules to produce a predictable result. In his "What Is Life?" lectures of 1943,(31) he claimed that the characteristic of life is that it seems to defy the rules of statistics. A very small number of molecules (statistically speaking), the genotype, predictably govern the structure and function of a whole organism, the phenotype. He claimed that "this situation is unknown anywhere else except in living matter."
The Second Law of Thermodynamics says that, in any process, the total amount of entropy (randomness) in the universe must increase. This is a direct result of the natural tendency of the universe toward equilibrium, a state of maximum disorder. Schroedinger wrote (31) "It is by avoiding the rapid decay into the inert state of 'equilibrium' that an organism appears so enigmatic." How, then, do we account for the processes of life, which seem to create order out of randomness? The answer lies in the fact that living things are open systems, that is, they exchange matter and energy with their surroundings. For every bit of order created within themselves, a greater amount of disorder is created in their surroundings. The process of building your body produces a great deal of heat, which causes the air around you to become more disordered. Thus, such processes stay within the bounds of the Second Law.
It is through the exchange of energy that life avoids the dreaded "equilibrium state". Therefore, life's "exquisite regulation of energy flow" (11) has often been included in its definition. One such definition includes the flow of energy within the organism, as opposed to between it and its surroundings: "Life is a group of chemical systems in which free energy is released as a part of the reactions of one or more of the systems and in which some of this free energy is used in the reactions of one or more of the remaining systems." (13) (The term "free energy" here refers to energy which can be put to use, as opposed to heat energy lost to the environment.)
Certain groups, particularly those interested in the possible nature of extraterrestrial life, consider the preceding definitions for life to be too limiting. For example, is it possible to differentiate between the individual organism and the entire biosphere? A bacterium could easily mistake a person for a huge colony of one-celled organisms working in symbiosis. One definition of life, from Feinberg and Shapiro's Life Beyond Earth (9), is "The activity of a biosphere." A biosphere they define as "A highly ordered system of matter and energy characterized by complex cycles that maintain or gradually increase the order of the system through an exchange of energy with its environment."
The presence of the now familiar terms of order, complexity, and energy should be noted. Reproduction is not required in this context. They propose that it might be more profitable for an organism to alter itself to adapt, rather than wait for randomly altered descendants to undergo the process of natural selection. In a perfect biosphere, with all elements in symbiosis, evolution of the parts tends to be detrimental. Consider the effect of cancer in a human.
Feinberg and Shapiro allow room in their definition for the existence of physical life, as opposed to chemical life. Examples they propose include plasma life, nuclear life, and radiant life. Plasma life, would exist inside stars, where interactions between charged particles and magnetic fields would create a self-sustaining, orderly system. One example of nuclear life would inhabit a very cold planet. It would be composed mainly of solid hydrogen and liquid helium. The spins, or magnetic orientations, of the hydrogen nuclei in the organism would be highly ordered. Magnetic fields caused by this organization of spins would induce further organization. Radiant life might inhabit interstellar nebulae, which are made of the dusty remnants of dead stars. This type of life is based on the properties of ordered radiation, using space dust as a tool for transforming the radiation. This can be viewed as an organized collection of self-stimulating lasers.
We have seen scientific definitions of life spanning quite a broad range. That "subtle combination of properties" has included structural features, growth, reproduction, metabolism, motion, response to stimuli, evolvability, information content and transfer, and control of energy flow. Obviously, the word has different connotations to different individuals. This will lead to confusion and disagreement unless the term "life", as suggested earlier by Dr. Marquand, is avoided by any discussion of "borderline systems". Leslie Orgel has coined the acronym CITROENS (Complex Information-Transforming Reproducing Objects that Evolve by Natural Selection (26) to describe certain of these borderline systems. Another acronym, SETI (the Search for Extra-Terrestrial Intelligence), deliberately evades the issue.
A less evasive way to prevent the confusion and disagreement is for the scientific community to hold a conference expressly for the purpose of defining life. Many of the criteria mentioned in this paper are not clear-cut, that is, they may be taken to varying degrees. So the line between life and non-life may indeed need to be drawn arbitrarily. Scientists often confer to draw such lines: How long should a meter be? Which reduction potential should be given a voltage of zero?
In the legal profession, terms and phrases used in criminal proceedings are carefully defined. Often someone's life or well-being depends on mere words in such cases. Scientists need to display the same rigor in defining their terms. It is one thing for the individual to be consistent in his or her terminology, but if all don't agree, communication between them will fail. Both attorneys must refer to the same dictionary.
Steve Potter, Philosophical Doctor
Caltech Division of Biology 156-29
Pasadena, CA 91125
spotter@gg.caltech.edu
potter.html