PICERAS

What is life? Biologists have long understood that life is very hard to nail down with any precise definition. Daniel Koshland, from the Department of Molecular and Cell Biology at the University of California, recounts the following story that nicely illustrates this:

What is the definition of life? I remember a conference of the scientific elite that sought to answer that question. Is an enzyme alive? Is a virus alive? Is a cell alive? After many hours of launching promising balloons that defined life in a sentence, followed by equally conclusive punctures of these balloons, a solution seemed at hand: “The ability to reproduce—that is the essential characteristic of life,” said one statesman of science. Everyone nodded in agreement that the essential of a life was the ability to reproduce, until one small voice was heard. “Then one rabbit is dead. Two rabbits— a male and female— are alive but either one alone is dead.” At that point, we all became convinced that although everyone knows what life is there is no simple definition of life. [Koshland, DE. 2002. The Seven Pillars of Life. Science 295: 2215-2216.]

Moving away from a reductionist definition, Koshland instead identifies seven universal principles inherent in all living things. He calls these the “pillars” of life. Since such pillars are features of life itself, and LUCA (the last universal common ancestor) would also be considered an expression of life (otherwise, it could not evolve into the three basic cell types), it seems quite reasonable to suppose that the same seven pillars would apply to LUCA. So what are they?

Koshland’s first pillar of life is a program. The program is the “organized plan” used to control the activity inside the cell as it persists through time. As he explains:

For the living systems we observe on Earth, this program is implemented by the DNA that encodes the genes of Earth’s organisms and that is replicated from generation to generation, with small changes but always with the overall plan intact…..It is in the DNA that the program is summarized and maintained for life on Earth.

It’s not the mere existence of DNA that matters, but its ability to encode a “program” that exerts control that matters. The second pillar, improvisation, complements the first pillar. Koshland notes that living systems need the ability to alter their program, as they cannot control the changes and vicissitudes of their environment. He explains that “such changes can be achieved by a process of mutation plus selection that allows programs to be optimized for new environmental challenges that are to be faced.” As we saw in the Design Matrix: A Consilience of Clues, this process of mutation and selection effectively serves the programming needs of the cell, a form of cybernetic evolution.

The third pillar is compartmentalization. Koshland views this from a biochemical perspective, noting that the cell’s membrane functions as a selective barrier, making it possible to maintain a chemical state inside the cell that is quite different from outside the cell. He then elaborates as follows:

The reason for compartmentalization is that life depends on the reaction kinetics of its ingredients, the substrates and catalysts (enzymes) of the living system. Those kinetics depend on the concentrations of the ingredients. Simple dilution of the contents of a cell kills it because of the decrease in concentration of the contents, even though all the chemicals remain as active as before dilution. So a container is essential to maintain the concentrations and arrangement of the interior of the living organism and to provide protection from the outside.

But compartmentalization serves the cell in another way. We can think of compartmentalization as a physical means of imposing modularity on the system, explaining why location is so important inside the cell. That is, a compartment can also be visualized as a subsystem. This modular arrangement of subsystems is also universal to life. And we know from engineering, that this is also a rational way of managing complexity, something already implied by the universality of the program. What’s more, the various subsystems can not function in a completely autonomous manner. As Arnold De Loof, a professor of zoology from Belgium noted, living systems are more than the sum of their parts because “the different levels of compartmental organization are interconnected by specific means of communication” [De Loof, A. 1999. Life as Communication. HMS Beagle Issue 68:]. Compartmentalization implies the communication of information in order to integrate the subsystems.

The fourth universal pillar is energy. We can think of energy as the ability to perform work, or better yet, as the ability to bring about specific changes. Since the cell is characterized by change, the requirement for energy is fundamental. Cells require and use energy to synthesize materials, move things around inside the cell, and to move molecules across their membrane and against a concentration gradient.

The fifth pillar of life is regeneration. Because life is characterized by constant interactions and constant change, the laws of thermodynamics entail that things will eventually break down. Thus, the living system requires mechanisms to repair and/or restore things to their original working state. As Koshland explains, “one such mechanism for regeneration is the constant resynthesis of the constituents of the living system that are subject to wear and tear.” He explains:

For example, the heart muscle of a normal human beats 60 times a minute—3600 times an hour, 1,314,000 times a year, 91,980,000 times a lifetime. No man-made material has been found that would not fatigue and collapse under such use, which is why artificial hearts have such a short utilization span. The living system, however, continually resynthesizes and replaces its heart muscle proteins as they suffer degradation; the body does the same for other constituents— its lung sacs, kidney proteins, brain synapses, etc.

In the Design Matrix: A Consilience of Clues, we saw that it was this very process of constant synthesis (or turnover) that solves the problem of breakdowns on the nanotech scale. Thus, while it may superficially appear wasteful for cells to continually assemble and disassemble their pieces and parts, it is this very flux that washes away the errors.

The second mechanism of regeneration is what we call reproduction. Koshland explains this nicely:

The constant resynthesis of its proteins and body constituents is not quite perfect, so the small loss for each regeneration in the short run becomes a larger loss overall for all the processes in the long run, adding up to what we call aging. So living systems, at least the ones we know, use a clever trick to perfect the regeneration process—that is, they start over. Starting over can be a cell dividing, in the case of Escherichia coli, or the birth of an infant for Homo sapiens. By beginning a new generation, the infant starts from scratch, and all the chemical ingredients, programs, and other constituents go back to the beginning to correct the inevitable decline of a continuously functioning metabolizing system.

In the Design Matrix: A Consilience of Clues we saw that a teleological perspective on reproduction allows us to envision it as a means to propagate designs through time. Reproduction is not something that “just happens,” but actually serves a purpose. Here we see the same theme from a different angle. By “starting over,” reproduction is like rebooting your computer when programs freeze or start to become sluggish. Such biotic rebooting is a complex, programmed event even in the simplest of cells. What’s more, because of the second pillar of improvisation, such rebooting events also entail the testing of possible solutions to solve the problems that caused the programs to freeze up in the first place. Evolution is not something that “just happens,” but instead is programmed into life.

The sixth pillar is adaptability. Koshland is not thinking in evolutionary terms here (that’s embedded in the second pillar), but in terms of particular organisms and their ability to process information about the environment and adapt to it. Strictly speaking, this is homeostasis. As Koshland explains, homeostatic responses “are a development of feedback and feedforward responses at the molecular level and are responses of living systems that allow survival in quickly changing environments.” To carry out such feedback and feedforward responses, the cell requires means of detecting the environment and converting such information into an intracellular signal. This signal must then be interpreted by some mechanism that can likewise control other mechanisms that will respond to the environmental change. The ability to detect, interpret, and respond are the three key ingredients in any organism’s ability to adapt to its immediate environment.

The last pillar of life is seclusion, something Koshland likens to privacy in a very busy world. Since living systems require a multitude of simultaneous reactions, there must be a way to impose some form of order on this activity, otherwise various activities will interfere with each other. One solution is found in compartmentalization. But seclusion is different method of imposing order, as explained by Koshland:

Our living system does this by a crucial property of life—the specificity of enzymes that work only on the molecules for which they were designed and are not confused by collisions with miscellaneous molecules from other pathways. In a sense this property is like insulating an electrically conducting wire so it isn’t short-circuited by contact with another wire. The seclusion of the biological system is not absolute. It can be interrupted by feedback and feedforward messages, but only messages that have specifically arranged conduits can be received. There is also specificity in DNA and RNA interactions. It is this seclusion of pathways that allows thousands of reactions to occur with high efficiency in the tiny volumes of a living cell, while simultaneously receiving selective signals that ensure an appropriate response to environmental changes.

Another way of thinking of seclusion is to think in terms of specificity, as it is specificity that allows for the seclusion of various activities. The components used by life must possess some minimum amount of specificity in order for a multitude of chemical pathways to be run simultaneously. Furthermore, it is this very specificity that allows the cell to control and regulate these pathways.

Koshland notes that the seven pillars of life (PICERAS) “are the fundamental principles on which a living system is based.” All seven pillars are intertwined with all living things, including all representatives of the domains Bacteria, Archaea, and Eukarya. Thus, either the last universal common ancestor of these three domains was also built around these pillars or the three domains independently acquired them. If the latter possibility is true, this would indicate that LUCA was front-loaded to acquire them. However, it is highly questionable whether life could even exist without one of the seven pillars. Take away the program and you take away the control. Take away the improvisation, and life quickly goes extinct. Take away the compartmentalization and there is nothing but a dilute, chaotic soup. Take away the energy and there is no means to maintain the living state. Take away the regeneration and the living state falls apart. Take away the adaptability and the living state is swept away by the wild contingencies of an uncaring environment. Take away the seclusion and you end with a short-circuited mess.

Yet if the seven pillars were also part of LUCA, this would indicate it was a rather complex entity. A common theme among most of the seven pillars of life is a means of dealing with complexity. The program is essential in the orchestration of complex events. Compartmentalization is needed to maintain a highly complex system through the integration of modular subsystems. Energy is required because, as Koshland notes, “the many reactions and the fact that there is some gain of entropy (the mechanical analogy would be friction), there must be a compensation to keep the system going and that compensation requires a continuous source of energy.” Regeneration is essential because complex systems are prone to breaking down. Adaptability itself is the expression of a complex, homeostatic reality. It would mean that LUCA was a cybernetic entity with the ability to sense its environment, translate that environmental information into a cellular signal, and respond accordingly. And seclusion is needed to prevent all the complex myriad of activities from cross-talking in a chaotic manner. Thus, by considering the various principles that define life, and assuming that LUCA was also an example of life, we have our first hints of a complex entity at the base of all known life.

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