True to Life?  Biological Models of Origin and Evolution

Martinez J. Hewlett, Ph.D., O.P.L.

Department of Cellular and Molecular Biology, University of Arizona, Tucson, Arizona

and

Dominican School of Philosophy and Theology, Graduate Theological University, Berkeley, California

Introduction

Erwin Schrödinger, after his participation in the founding of quantum mechanics, turned his attention towards the life sciences.  In "What is Life?", his self-described "little book" he wondered about what the physical character of the gene must be.[1]  It struck him that the nature of heredity is such that, whatever the chemical material of the gene might be, it resists the thermodynamic imperative of the second law towards dissolution.  In his book, he focuses on well-known examples of strong inheritance, such as the famous Hapsburg lip.  His speculation leads him to suggest that there may, indeed, be new physical principles or even laws waiting to be discovered.

His musing had a profound influence in at least one young physicist.  Max Delbrück would take up this quest and become a guiding light in the new discipline that would bring the quantitative approaches of physics and genetics to bear on discovering the chemical nature of the gene.  The birth of molecular biology and Schrödinger's influence on Delbrück are recounted in a delightful and recently updated festschrift volume called "Phage and the Origins of Molecular Biology."[2]

What is Life?

The question that occurred to Schrödinger and that motivated Delbrück is perhaps to simple for our purposes.  Rather, like the proverbial newspaper reporter, we need to ask for the complete story – the who, what, when, where, why and how of life.

In order to do this, we need to acknowledge that not all of these questions are properly within the domain of science and that some of these may be metaquestions for biology.  Let me offer the following table as and explanation of what I mean by this.

The first four questions in this table lead to investigation space that is clearly within the realm of the science of biology.  The last two questions — the what and why questions — lead, instead, to philosophical and perhaps theological investigation space.

The standard hierarchy of biology can be viewed as a road map to the answers for the first four of these questions.  The hierarchy in this model begins with biological molecules as chemicals (biochemistry), moves to biological molecules as information (molecular biology), and progresses on through cellular biology, organismal biology and finally arrives at the study of populations of organisms (ecology).  The overarching paradigms of Darwinian evolution and Mendelian genetics are considered to operate at each of these levels, thus producing the neo-Darwinian synthesis, as I will discuss in a moment.

One way of interpreting this hierarchy is to assume that the reductionism is operative, both methodologically and causally at all levels.  It is my purpose to examine this assumption in the light of the types of emergence discussed in this volume.

I will ask two general questions:

•  Is life an emergent property of non-life?

•  Is complexification an emergent property of life?

I will present the current biological models that attempt to address these two questions.  I will then discuss future directions in biology, with a focus on models that may challenge the current underlying philosophy of the discipline.

Life From Non-Life

Prebiotic Simulation Models

In 1953, Stanley Miller, then a student in the laboratory of Harold Urey, reported on an attempt to simulate the prebiotic conditions on earth and to look for the synthesis of organic molecules under these conditions.  He placed methane, ammonia, hydrogen, and water in a flask and repeatedly introduced an electric spark to simulate lightning in the atmosphere of the primitive earth.  He was able to recover organic molecules from this experiment, including some forms of amino acids, the subunits of proteins.[3]  These results were based upon the assumption that the primitive earth would have a reducing atmosphere in which organic molecules could form in the presence of electric discharge.

In no way, however, can it be said that these molecules were living, although this experimental approach did much to support the notion that at least the chemicals necessary for life might have been present on the pre-biotic earth.  These kinds of experimental approaches continue at present, with an emphasis in exobiology, the study of the possibilities for life in places other than this planet.

The Miller experiment and those deriving from it opened the debate about what the earliest “living” molecule might be.  Although the precursors for proteins are found under these conditions, no one could imagine how proteins would eventually become self-replicating.  Proposals were made that would allow living systems to form on the surfaces of silicates, with this surface acting as a catalyst for the reproduction of pre-biotic proteins.  However, it was a discovery related to the processing of information in eukaryotic cells that changed the model.

Self-replicating Models

Tom Chech and Sid Altman were among four who received Nobel Prizes (two in medicine and two in chemistry) for work related to how informational RNA molecules in the nucleus of eukaryotic cells are processed before being delivered to the cytoplasm for translation into proteins.  Part of the sequence of steps includes the removal of certain segments of the RNA through a set of reactions called RNA splicing. Chech observed that some of these reactions are catalyzed by the RNA itself in an event called self-splicing.[4]  This led, in turn, to the notion that RNA molecules can catalyze the kind of reactions that take place within cells.  The ultimate function, however, is self-replication.  Such self-replicating RNA molecules have indeed been described several times.[5]

The idea that RNA can self-replicate leads to the notion that some kind of RNA might be a good model for a pre-biotic molecule.  If such molecules could form under conditions present early in the history of the planet it could be that replication becomes a selectable property that would allow further propagation of the structures.  This has been termed the RNA world and, for a while, dominated the thinking about origin of life and exobiology.  More recently, however, the popularity of RNA for these models has waned.  No one has been able to set up prebiotic conditions in which RNA can be isolated.  Since it is an inherently unstable molecule, the likelihood of its occurrence in such systems is quite slim.  At this time, proteins have come back to the fore, especially as discussed by Manfred Eigen in his influential book, "Steps Toward Life."[6]  The currently favored model is one in which both protein and nucleic acid formed during the prebiotic stage, preceding the formation of cellular life.

Spontaneous Order Models

In deciding how such molecules formed, the problem seems to be one related to the thermodynamics of the situation.  How can it be that complex structures that can self-replicate would occur in the face of the loss of entropy that this would entail?  Stuart Kauffman of the Santa Fe Institute has tackled this problem and has described his conclusions in "Origins of Order."[7]  Kauffman proposes that prebiotic molecules are such that they will spontaneously increase in complexity, without any violation of thermodynamic principles.  Remember that the second law applies to closed systems and molecules in prebiotic environments are, in fact, open and exchanging energy with the environment.  Kauffman's view is that order emerges from the very properties of the molecules.

Kauffman and other complexity specialists such as Chris Langton (see his paper in this volume) argue that the most interesting transitions occur in systems that are at the edge of chaos.  It is under these conditions that life might have developed.

As a virologist, I have studied organisms that seem to exist at the boundary between the living and non-living world.  I use the term “organism” to describe a virus.  This is, of course, argumentative.  The simplest virus particle consists of a protein shell and a nucleic acid genome.  Viruses carry out certain key functions that we associate with life, such as replication, transmission of genetic information to new generations, and formation of complex structures.  However, they do not carry out metabolism.  In fact, as obligate intracellular parasites, they rely completely on their host cells for all metabolic processes and energy generation.  And yet, they occupy an important place in the biosphere.  Are they living or non-living?  Certainly, if we consider agents such as viroids (self-replicating, infectious RNAs) or prions (self-replicating proteins), then viruses seem quite alive indeed.

The Complexity of Life

While biologists struggle with modeling how life arose initially on this planet, the fact is that life does exist, in all of its glorious complexity.  My second questions bears on this observation:  is complexification an emergent property of life?

For biology, the 19^th century saw two major achievements:  Darwinian evolution and Mendelian genetics.  Although initially no one realized the relationship between them, they would be brought together in the 20^th century in the neo-Darwinian synthesis.

The Darwinian Model

Darwin's great achievement was the recognition that the complexity apparent in the living world could be explained by descent with modification from a common ancestor.  He argued that the driving force of this process would be natural selection, favoring those organisms best able to reproduce in a given environment.

The evolutionary biologist John Maynard Smith defines the Darwinian model as follows[8]:

These four principles are often summarized as "descent with modification."  Notice that this model stresses the reproductive fitness of the variants, such that they are more likely to pass on their characteristics to offspring.

The Darwinian Model and Theodicy

The identification of evolution with the phrase "survival of the fittest" occurs in Darwin's 6^th edition of his book.  In Chapter III of this version, Darwin states:

I have called this principle, by which each slight variation, if useful, is preserved, by the term natural selection, in order to mark its relation to man's power of selection. But the expression often used by Mr. Herbert Spencer, of the Survival of the Fittest, is more accurate, and is sometimes equally convenient.[9]

This view of evolution as a fierce competition has been poetically linked to a line penned by Alfred, Lord Tennyson some nine years prior to the publication of Origin of Species:

"Who trusted God was love indeed

And love Creation's final law—

Tho' Nature, red in tooth and claw

With ravine, shriek'd against his creed—"

Darwin himself was affected by the apparent ruthlessness inherent in his model of natural selection.  In an 1860 letter written to the American botanist, Asa Gray, Darwin said:

The observation is compelling.  The Ichneumon wasps are parasitic and lay their eggs within the body of certain caterpillars.  There, the larvae develop and grow, using the live caterpillar for sustenance.

However, this is not the complete picture.  Darwin was not aware of observations made recently.  In reality, when the wasp lays her eggs in the caterpillar, the immune system of the caterpillar most often destroys the larvae before they can develop.  Some female wasps are infected with a polydnavirus that resides in their tissues with no negative effect on the insect.  The virus is injected into the caterpillar along with the eggs.  This virus then infects the tissues of the caterpillar, interfering with the immune system and allowing the wasp larvae to grow.[11]

Does this mollify Darwin's problem?  Certainly when one looks at the individual case of a particular wasp and caterpillar, it seems hard to justify.  However, on the larger scale, at the level of the two species, one could argue that the system of the wasp, caterpillar, and virus is balanced so that all survive.  While this does not rescue the theodicy problem that Darwin raises, it certainly casts the issue in a different light.

The Modern Synthesis Model

By the middle of the 20^th century, Julian Huxley could boast of the modern synthesis, also called the neo-Darwinian synthesis.[12]  In this welding together of the sciences of Darwinian evolution, Mendelian genetics, and biochemistry, scientist found a series of tools that have resulted in the paradigms of the hierarchy I discussed earlier.  The features of this synthesis include:

• Genes:  information in the form of the linear array of bases that make up the DNA molecules of chromosomes.

•  The traits of an organism (phenotype):  direct expression of the information found in the genes (genotype).

•  Variations:  result of subtle differences in this information (changes in base pairs).

•  Changes in genes:  mutational events that occur in a “random” way.

•  A population of entities:   will have variations in traits that are the result of mutational events (genetic drift).

The force of natural selection operates on this pool of genetic variants, allowing those with greater reproductive fitness to be represented in succeeding generations.  The model emphasizes strict gradualism, whereby mutations occur in small steps, usually one base pair at a time, over long, geological periods.

The force of this synthesis is such that it is difficult to think of any biological problem with reference to its principles.  It is important to note, however, that the synthesis retains much of the 19^th century philosophical underpinnings of both evolution and genetics.  As a result, modern biology tends towards reductionism and determinism, in the Newtonian framework that was operative for both Darwin and Mendel.

This orientation can be seen in the work of many contemporary evolutionary biologists, including Richard Dawkins and Edward O. Wilson.  In "The Blind Watchmaker," Dawkins argues for gradual change and natural selection leading to all of the existing forms of life, focusing on the central role of DNA in the scheme.  He writes that "... living organisms exist for the benefit of DNA rather than the other way around."[13]  In a similar vein, Wilson proposes that genes play a pre-eminent role, even in the development of human behavior and culture.  He argues that environment is important in the selection of genetic variants and in their expression.  In the end, however, it is the gene and its information the determines who we are and what we do as humans.[14]

Both of these positions assume a reductionistic and deterministic foundation.  Even though allowances are made that allow some higher level patternings, these are really epiphenomenon of the structures that make up the whole.  Dawkins, in fact, defends this assumption by renaming it "hierarchical reductionism."  He says that “reductionism, in this sense, is just another name for an honest desire to understand how things work.”[15]  His statement does not reveal any understanding of the philosophical issues at stake, conflating as it does the methodological approach of science with the epistemic and ontological conclusions he then makes.

Is the Darwinian model then irretrievably embedded in this philosophical system?  Some aspects of modern biology, such as the Human Genome Project, would argue yes.  On their web site, one can find a slide that touts "from DNA to humans" as a kind of working model.[16]  On the other hand, no one working in biology disputes the complex nature of life and the levels of organization observed.

The late Stephen Jay Gould was a most prolific writer concerning issues in evolutionary biology.  His contributions to the field included two that continue to be controversial among the strict gradualists such as Dawkins and his interpreters.  These are punctuated equilibrium and the notion of spandrels.

The Punctuated Equilibrium Model

As Gould states in his final majestic work on evolution, he and Niles Eldridge were led to their proposal of punctuated equilibrium by the "species problem."[17]  Using the gradualistic approach (also called anagenesis) one assumes a continuum of change over deep time.  The problem arises when one needs to assign boundaries between populations.  Is this done arbitrarily or are there some defining features that allow such an assignment?  As an alternative explanation, Gould and Eldredge proposed the concept of punctuated equilibrium.[18]  In Gould's most recent description of this theory he writes:

… Eldredge and I argued that the vast majority of species originate by splitting, and that the standard tempo of speciation, when expressed in geological time, features origin in a geological moment followed by long persistence in stasis.[19]

The critics of this model are champions of gradualism as the principal, if not only mechanism, by which evolution takes place.  Dawkins, for instance, caricatures punctuated equilibrium as anti-Darwinian.  He argues that, since the suddenness in the theory is really over geological time scales, there is no difference here.  However, since Dawkins is a strict gradualist, he also argues against the rapidity of change that would be required for punctuated equilibrium to be true.

Nevertheless, Gould and Eldredge have had a significant effect on evolutionary thinking, if in no other way than to decrease the reliance on the gradualist approach.  Does punctuated equilibrium alter the reductionistic setting in which modern biology finds itself?  In general, the answer would be no, since there is no change here in the emphasis on the gene as the determiner of traits.  However, since Gould and Eldredge rely on speciation rather than gradualism, there is a consideration of natural selection acting on the organism level.  Their theory proposes that animals can be reproductively isolated by environment and geography, thus creating a population that can rapidly evolve into a different species.  This model leans away from the single steps of the gradualist towards a macroevolutionary framework.  Dawkins discounts the importance of macromutational events, but I will return to these below.

The Exaptation Model

If punctuated equilibrium was not enough to set his critics on edge, certainly Gould's next proposal more than drove them over that edge.  In 1979, Gould and Richard Lewontin published the paper that introduced the concept of spandrels into the literature of evolutionary biology.[20]   Gould and Lewontin attack the standard adaptationist approach of evolutionary biology as "panglossian," or what Gould had come to call "just so stories."  They used the architectural model of spandrels to explain their reasoning.  A spandrel (or pendentive) is a somewhat triangular space that is found between two adjacent arches in medieval cathedrals.  It is actually best thought of as a space left over.  Gould and Lewontin refer to the wonderful mosaics of the four evangelists adorning the spandrels in the great cathedral of St. Mark in Venice, Italy.  They point out that you could assume the spandrels were put there to contain the art, when, in fact, they are really necessary features required by the use of arches to support a dome.  In the same way, they argue, certain features of organisms are dictated by the ways in which living systems develop, in accordance with physical principles.  Such structures are then used by evolution because of the advantages they confer.  As they wrote in their paper:

...organisms must be analyzed as integrated wholes, with baupläne so constrained by phyletic heritage, pathways of development, and general architecture that the constraints themselves become more interesting and more important in delimiting pathways of change than the selective force that may mediate change when it occurs.[21]

The reference here to organisms as "integrated wholes" is in clear distinction to the reductionistic approach favored by the gradualists.  Gould by no means intended spandrels to be seen in the same light as those structures touted by intelligent design theorists as "irreducibly complex."  Rather, Gould envisioned spandrels as nonadaptive structures that set constraints on the ultimate structure of an organism and that can be co-opted for use in an evolutionary pathway.  He coined the term exaptation for this kind of evolutionary use in order to distinguish it from adaptation.[22]

Do these biological models imply that complexification is an emergent property of life?  Certainly a strictly neo-Darwinian model would point strongly in the direction of causal reductionism.  As we move toward the models presented by Gould, however, biology appears to be more amenable to thinking holistically and allowing space for emergence.  The idea of nonadaptive structures such as spandrels setting boundary conditions for living systems is at least tending towards emergentism.

New Models and New Directions

How are these models changing?  More importantly, what kinds of evidence are accumulating to press for change?  We can ask these questions in the Kuhnian sense, in that explanatory problems arising from the current paradigms in the field are what drive the need for such re-examination and change, if warranted.

Sources of Mutational Change

First, it is important to realize that the gradualist ideal of single step changes, championed by Dawkins and others, is only one kind of genomic change that is observed.  Lynn Margulis has summarized the array of hereditary alterations that are observed.[23]  The following table is adapted from her paper.

The first column includes those kinds of genetic changes that would be called gradual, single-step alterations, occurring one or only a few bases at a time.  These micro-hereditary alterations are what Richard Dawkins believes to be the principle source of variation upon which evolution acts.  However, the macro- and mega-hereditary changes referred to in the table play significant roles in observed variation.  In some cases, such changes appear to have led to alterations that have had quite sudden consequences.

The Origin of Eukaryotes

Lynn Margulis proposed that eukaryotic cells, that is, cells with internal, membrane-bound organelles, originated by an endosymbiotic relationship between two or more ancestral cells.  While echoes of this model can be found in earlier literature, it was Margulis who most clearly articulated and defended this endosymbiotic model.  Her explanation is a model for the existence of the energy generating organelles, the mitochondria and the chloroplasts.

Recently, Chris Langton and I have been concerned about this model and its predictive value for the existence of other eukaryotic intracellular structures.[24]  In particular, we considered the endomembrane system of the cell, involved in the synthesis and movement of proteins throughout the cell.  We modeled the origin of this membrane system as a network of interacting cells, living in a parallel symbiotic relationship and sharing functions by export through the extracellular space surrounding the network.  Over time, the relationship of this network or colony of cooperating cells becomes a selective advantage.  Note that, in this case, the selection is for an emergent property of the system – the relationship in the network.  In our model, the cells involved in the cooperative colony come to interact even more closely until, finally, the colony fuses into one cell.  In this model, what was the extracellular space between the cells becomes the intracellular endomembrane system involved in moving proteins from one location to another.  Our model explains the observation that the topology of the endomembrane system in the eukaryotic cell is such that the interior (lumen) of the endomembrane system is topologically equivalent to the outside of the cell.  Thus, using a strictly Darwinian notion of selection for reproductive fitness, our network evolves into the eukaryote, able to expand into new ecological niches because of its increased metabolic potential.  Selection here has been for an emergent property of the colony, the interactions between the cells.

Scale-free Networks and Biological Systems

Of course, networks have been known for a long time.  However, it is only recently that the nature of the interactions in a network has begun to be explored.  Several recent texts of both scientific and general interests have been published about what is being called the new science of scale-free or small world networks.[25]^,[26]  Most interestingly, the kind of network termed "scale-free" has properties such that the network is more than the sum of its parts.  When the number of connections between nodes in a regular network is plotted versus the number of nodes, a typical distribution over a particular range is obtained.  However, for scale-free networks, such is not the case.  In these networks a few nodes are highly connected, leading to a plot that, on a log-log scale, is linear of a large range of values.  Theses networks are also called "small world" in recognition that one of the first observations of this kind of behavior was in human social connections, published in 1967 by Stanley Milgram.[27]

Scale-free networks exist at all levels of organization, from the network of interacting proteins within the cells of an organism,[28] to the colonial organization of social insects,[29] to the World Wide Web,[30] and finally, to the network of human sexual interactions.[31]

This later example is quite interesting.  In epidemiology, viral infections are characterized by a certain threshold of infection.  Below the threshold, it is unlikely that the virus will spread in the population, while above the threshold the virus will spread.  Influenza viruses are typical of this pattern.  In contrast, human immunodeficiency virus (HIV), the causative agent of AIDS, spreads in the human sexual contact network.  In this kind of scale-free network, HIV has a zero threshold for spread.  This means that once the virus enters the network the chances of spread are 100%.  This is a startling result that has major implications for the control of AIDS in populations.

The scale-free properties of these networks are emergent.  That is, it is not the nodes that produce these properties, but the relationships and connections between the nodes.  Therefore, the network as a whole cannot be understood by simply summing the parts.  Such networks are not methodologically or philosophically resolvable by reductionism.  In fact, reductive approaches lead in the opposite direction. Albert-László Barabási, in his recent text on this topic, humorously points out the limits of the reductive approach in this case:

Barabási continues with a critique of reductionism and a defense of emergence.  To place this in perspective, it must be said that Barabási is a physicist.  It would seem, from these examples, that the science of scale-free networks presents a potential shift in the philosophical perspective of the sciences, including biology.  This shift is being driven, I maintain, by the failure of the explanatory power of the reductionist approach to complex systems.

Conclusion

Science is about building models of reality.  These models are based upon paradigms that underlie the discipline at any given time.  The strength of these models depends upon their explanatory and predictive power.  Here, I mean predictive in the sense of generating additional experimental approaches.

The models that are used in biology rely both on the observations being made and on the philosophical setting in which these observations take place.  Until recently, models based on a strictly reductive methodological and epistemological approach have been extremely productive.  However, as more and more complex systems are analyzed, it has become clear that the value of such models is limited.  As the concept of emergent phenomena gains greater acceptance, models that incorporate higher order levels of organization will become increasingly important.

What does this mean for the science/theology discussion?  On the one hand, as science begins to be philosophically oriented away from the strictly reductive view, a pathway can be seen that might allow intellectual acceptance of such non-material issues as consciousness and spirituality.  On the other hand, there remains the divide between physicality and spirituality that may continue to limit investigative exchange between these two fields.

References