Only from this engineering perspective can we understand the physicochemical system that is a cell in space and time, putting aside the question as to its origins. In general, engineered objects must fulfil a function, for which they need instructions e. Traditional molecular biology tends to forget the distinction between function, instructions software and operating system , and machinery to execute them hardware. A machine of this type can be adapted to perform all kinds of operations, including self-assembly.
Taking this metaphor to the extreme, cells can be understood as computers that make computers Danchin, a , not unlike 3D printers that build other 3D printers Bowyer, The statement biology-as-engineering nonetheless requires several nuances.
First, looking at biological objects as if they were the product of engineering says nothing about the intervention of an engineer. Whereas the former is not within the realm of science, the latter is an extremely useful interpretive frame to understanding why biological systems are as they are and not different.
For the same reason, engineering can be adopted as a metaphor and a hermeneutical lens to understanding the logic of biological objects, which is different but perfectly compatible with other explanatory keys that address unlike questions. As sketched in Fig.
The interpretive frame of synthetic biology for understanding how live systems work. By the same token, the appearance of design what I call technonomy is an invaluable conceptual asset to make sense of the relational composition of live systems that makes them work—without adopting any belief beyond that e.
Apart from these somewhat speculative arguments, can we really consider living systems from the viewpoint of an engineer? None of the materials has a precise function originally, and each can be used in several different ways. This view nonetheless appears to say that the structure of living systems has no relational logic comparable to engineering. But taking the tinkering metaphor to an extreme, one could end up in a situation not unlike those of humorous Rube Goldberg machines i.
But a candid inspection of data, in particular on the application of synthetic biology approaches for understanding extant biological devices could suggest otherwise. Although different paths can lead to different solutions for design problems, the outcome frequently coincide or converge and one approach can easily help to understand the other.
It is not only the wings of planes, birds and bats, but also intricate mechanisms of process control in countless biological objects Steel et al.
Rube Goldberg machines: simple operations run by complex gadgets. Rube Goldberg — was an American cartoonist popularly known for a series of satirical drawings describing very complicated devices. In the example shown, the simple objective of waking up a gentleman in the morning is disclosed as a chain of 15 events A-P run by spare components in which the outcome of each of them triggers the next one. The same can apply to live systems; although their structure and function cannot be attributed to an engineer, it is very useful to examine them with the perspective and formalisms supplied by engineering.
Functions and biological modules that constituted an evolutionary innovation to solve a problem were most successful when they were later assimilated into another context in response to another challenge. For example, when plumage appeared it was merely thermal insulation of dinosaurs, but later became an essential component of bird flight.
The analysis of bacterial genomes provides numerous examples of proteins that do something now that turns out to be very different from that for which they originally arose. Functional co-option is in fact very frequent. For instance, extant transcription factors often evolved from enzymes that used as substrates small molecules that later became effectors of the thereby evolved regulators.
Also, the same regulatory proteins e. This process, which in evolutionary biology is termed exaptation , also has innumerable engineering counterparts: a device invented for a very specific purpose reappears elsewhere with minor modifications and an unexpected function.
The system for rapid loading and release of bombs in combat aircraft can be reused for incorporation and replacement of heavy batteries in electric cars Senor and Singer, The re-adherable glue borne by Post-it notes was first discarded as a too-weak adhesive until it found a very successful function as a press and peel bookmark.
An innovation born for one function can triumph when it is assigned another purpose, different and even opposite the original. This scenario appears constantly in biological and in designed systems, reducing what Jacob saw as an insurmountable gap between the two.
It will nonetheless be difficult to hold a calm debate on the principle of techno-nomy proposed here at a time of confrontation between evolutionism and intelligent design, which became a focal point for heated public debate in the USA and has echoed elsewhere.
Coming from a different culture, such a confrontation is not only somewhat farcical but also misleading for tackling the issue of origins vs. Human intelligence is in itself the result of evolution and therefore objects rationally designed by conscious minds might be often indistinguishable from those resulting from a random exploration of a solution space—as they are both obliged to undergo a multi-objective optimization process see below.
Biological evolution and meta-evolution e. Note also that whether evolved or engineered, the outcomes may both be plagued with imperfections and suboptimal solutions that rational design most often produces as well. It may thus be difficult to distinguish whether a given functional item is the result of blind evolution, amateur bricolage or smart design: they all are about finding the same optimal attractors in a solution space through different itineraries. This is something for celebration and one of the most useful contributions of synthetic biology to the scientific research of live systems.
Looking at biological phenomena through the lens of engineering has the same potential to transform the field as did looking at biological phenomena through the lens of physics in the post-war period, which led to the birth of molecular biology. A second qualification of the biology-engineering relationship has to do with the modular structure of the objects of study in each case. Any entity designed by an engineer is composed of clearly defined modules, with connectivity between its well-standardized components which allows re-use in different contexts , with compatible inputs and outputs and a clear hierarchy and three-dimensional arrangement of the various components.
This matches the physical and the functional modularity of objects made by the engineers, at least approximately. In contrast, existing biological systems do not at first glance seem to express this coincidence between the physical and the functional. By comparing groups of persistent genes in microbial genomes, the catalogue of functions necessary for a living system has been calculated at about — de Lorenzo and Danchin, A search for specific genes shared by these same genomes nonetheless leads to the surprising conclusion that this number is exactly zero Acevedo-Rocha et al.
This means that the same functional needs of live systems can be met by very different configurations of genes and molecules. Footnote 3. Another remarkable detail that separates designed objects and biological systems are the physical characteristics of their components: telephones and aircraft are made of hard materials, with parts whose three-dimensional structure is clearly defined and has precise connections to neighbouring pieces.
Unforeseen interactions often cause problems and cause accidents. In contrast, biological objects are typically composed of soft elements, sometimes without clear boundaries and a tendency to interact with one another, which at times leads to the emergence of unanticipated properties.
If electrical and industrial engineering consist of cables, tubing and screws, living systems are composed of elastomers, gels and glues. Finally, living systems grow, replicate, and reproduce: properties alien to the rationally engineered objects we know.
Does this mean that the principle of modularity we associate with man-made devices is absent in biological systems? Again, the answer is no. The complexity of cells with large genomes and extensive biochemical diversity is misleading in this regard.
Analysis of the minimal genomes of endosymbiont bacteria, for example, shows a considerable degree of modularity in the essential functions that allow their existence Porcar et al. The biochemical soup that metabolism sometimes appears to be is in fact perfectly modularized, with an organization reminiscent of a chemical factory de Lorenzo et al.
Neither is the idea of self-replicating objects new in engineering, as shown by attempts in the last decade to design three-dimensional printers that print themselves e. It is therefore as possible and productive to use the metaphor and even the formalisms of engineering to understand the function of biological systems as it is to use the biological metaphor to guide the design of new man-made devices.
A good part of contemporary engineering is accustomed to randomly exploring the space of solutions to a problem that cannot be resolved by first principles because of the many parameters involved i.
The interesting thing here is that these solutions to e. It therefore seems that, in engineering as in biology, the space of solutions to an adaptive challenge is neither homogeneous nor it has an infinite number of possible outcomes. Instead, it has attractors i. One conspicuous case of strategies akin to typical adaptive processes of biology for addressing a multi-objective optimization challenge was the design of antennas ST5— and ST W which were deployed in a NASA spacecraft in Lohn et al.
The evolutionary algorithms Coello et al. This shows the value of evolution in shaping optimal devices and vice versa : the utility of examining the logic of living systems with the conceptual tools of engineering. It is no surprise that experimental evolution is increasingly merging with synthetic biology. Recent examples include the adaptation of E.
But many more examples are in the pipeline: what many call experimental evolution or evolutionary engineering is in fact an extreme case of multi-objective optimization but involving too large a number of parameters for being rationally tackled—for the time being.
Non-numerical multi-objective optimization. Builders of intricate structures before the scientific era were often faced with the need to play a large number of parameters that were not amenable to the calculation tools available at the time. Architects like Antoni Gaudi — figured out ways to solve the problem by making string models of the building or building parts a in which weights were hanged at critical places for revealing the effect of local structures on the geometry of the whole object.
Sequence diversification at such regulatory points and selective pressure to increase production of Z allows exploration of the solution space until an optimum is reached.
Development of NASA antennas through evolutionary algorithms. The option for engineering as a key to interpreting the biological phenomena that define synthetic biology has a derivative as fascinating as it is unsettling. It is not just an epistemological question, but also very practical. If a biological system is like an engineered artefact, then we can also dismantle it into a limited set of defined components that we can then recompose to generate a different object based on a rational plan.
The result can be an object whose structure and properties differ from those of the original source of its components. To do this we require two things. First, we need the relational and hierarchical abstraction of the new object as a set of parts the basic units of biological function that are connected rationally to form devices, and these in turn to generate systems of increasing complexity.
At this point, we jump from engineering as a metaphor and analogy as in genetic engineering to engineering as a genuine method for constructing biological objects. In second place, the parts for engineering new biological systems must be standardized to make them reusable, composable and scalable.
In most cases, these parts do not appear this way in their natural situations. We can make a hut with tree trunks just as nature offers them. But to build a house the logs must become beams and panels of precise dimensions that allow the construction of a more complex building Porcar et al. By this reasoning, one characteristic of synthetic biology is the effort to start from DNA sequences that determine desirable functions and modify them for use as building blocks e.
Bio-Bricks for new biological objects Kosuri et al. Based on the existing situation, one can think of modularizing biological functions and components more and more to make them easier to combine, both physically and functionally. A bacterial promoter that, in its native context, controls expression of a tetracycline resistance gene when the cells encounter the antibiotic in the medium is converted by the artistry of synthetic biology into an inverter module a NOT gate in logic that can be combined with others to perform calculations and process signals not originally their own Silva-Rocha and de Lorenzo, Various bacterial and plant enzymes can be assembled in yeast to give rise to the biosynthetic pathway of an anti-malarial drug Paddon and Keasling, Protein anchor sites derived from metazoan signalling pathways have been used in Escherichia coli to channel the substrates for a biotransformation of industrial interest Dueber et al.
And so on, in hundreds of cases in which a biological function is decontextualized using recombinant DNA tools and more recently by chemical synthesis of DNA sequences and reused in another situation to do something that nature has not done or invented. This endeavour faces two major challenges. The physical composition of DNA sequences does not necessarily translate into an integration of the corresponding functions, at least quantitatively.
In addition, the parameters associated with the biological parts promoters, terminators, ribosome binding sites often change with host genomic context and physiological conditions. Indeed, the problem of context dependence is one of the major limitations in the design of reliable biological devices.
Several lines of action have been proposed to remedy this state of affairs. One of these approaches is to edit the genome and eliminate all complexity not strictly necessary for a given application.
This might be followed by elimination of unused metabolic blocks, cell envelope structures and many other genes that might be deemed unnecessary. This approach could ultimately result in a minimal genome Vickers, and thus simplify the molecular context of any device that could be implanted in it. Yet, attempts to reduce the genome of model bacteria such as E. Apart from the elimination of possible essential genes, deletion of large chromosome segments could alter its architecture within the cell, making it unviable.
An alternative is to proceed in exactly the opposite direction, starting with bacteria whose genome is already very small, such as Mycoplasma or endosymbionts like Buchnera Roeland et al. In these cases, nature itself has made the reduction. Although this can be a good approach in principle, that a system has fewer components does not mean that the outcome will be simpler.
Reduced compositional complexity is compensated by an increase in relational complexity; chromosomes with fewer genes give rise to cells that are much more dependent on interaction with the environment. Even so, some bacteria with small genomes such as Mycoplasma have become models of reference in synthetic biology, particularly because their chromosome size permits complete chemical synthesis, as done by the Venter group Hutchison et al.
This enables implementation of the scenario above, considering bacteria and other biological systems as computers for which software DNA can be written and applied by existing molecular machinery. But simplifying the genome and even rewriting it completely does not solve all the problems. As mentioned above, the operation of biological parts, especially quantitative, is subject to varying degrees of influence at various contextual levels —from interference from nearby sequences to general and environmental effects.
To the benefit of evolution, but to the irritation of bioengineers, biological materials proteins, polymers, small molecules tend to interact with their molecular neighbours in often unpredictable ways. A situation familiar to any biotechnologist is uncertainty regarding the efficiency of heterologous expression systems for genes of industrial interest.
This is often the case, but on occasion the opposite is true Kosuri et al. Two systems are mutually orthogonal if they do not influence each other. It is conceivable to start from a very connected biological component or module to produce a variant that retains only the desired connectivity, thus facilitating its use for new biological designs.
Nature itself offers cases of orthogonal parts, typically in promiscuous mobile elements and bacteriophages e. But great progress has also been made in developing alternative genetic codes and orthogonal ribosomes able to decipher them.
Perhaps in the not too distant future we can have biological entities with a genome that encrypts information with a distinct genetic code even using non-natural bases; Malyshev et al. The larger and more dominant cowbird chicks often survive at the expense of native species, driving declines in songbirds across North America.
Some species, however, have evolved defenses. For example, songbird species with a longer history of exposure to cowbirds are more likely to recognize and reject cowbird eggs. This has led Kilpatrick and others to ask whether in some cases management efforts may be getting in the way of evolutionary progress.
But by reducing the threat of nest parasitism, managers also reduce the selective pressure for an adaptive response. But there is another kind of risk—management dependency that has no stopping point. Martin Schlaepfer and two co-authors took up this theme in the journal Ecology Letters 3. Schlaepfer, a conservation research fellow at the University of Texas, Austin, had been inspired by the Stockwell et al.
This often occurs when foreign species invade new habitats. For native snakes in Australia, Schlaepfer explains, the strategy of viewing any frog-like creature as potential prey became a liability.
Toxic cane toads, introduced to Australia in the s, are poisonous enough to kill many snake species in a single meal. In fact, researchers have estimated that cane toads threaten up to 30 percent of terrestrial Australian snake species.
Similarly, monarch butterflies incorrectly perceive the nonnative black swallowwort as a suitable host plant for egg-laying, although toxins in the plant prevent the monarch larvae from developing.
It is often impossible to undo changes that cause species to be caught in evolutionary traps. But such species may be particularly good candidates for evolutionary rescue. A simple shift in behavioral response or an incremental improvement in defenses may solve the problem.
Modeling studies suggest that adaptive shifts are more likely when selective pressures vary from strong to mild in different locations. By manipulating habitat, Schlaepfer says, managers might create just such an evolutionarily productive mix of refuge zones and areas of strong selection. Schlaepfer, Kinnison, and others are also talking about taking evolutionary management a step further—not just helping species survive long enough to adapt, but actively manipulating their genetic composition to speed adaptive change.
In theory, at least, the ability to influence the number and even the type of genetic variants present in a population would give researchers a leg up on nature in driving evolution.
Conservationists already manipulate gene flow when they connect isolated populations through habitat corridors or maintain barriers to prevent hybridization. But the goal of such efforts has been to preserve gene pools i. In the latter context, the trick is to determine the proper dosage of genetic variation. Not enough, and selection may have little to work with because the chances of a population containing genes for disease-resistance, for example, go down.
Too much, however, and adaptation may be thwarted. To see how this might play out, consider the plight of a plant species threatened by global warming.
Adaptations that might ultimately help the species survive are most likely to originate in the southern portion of its range, where conditions are already hotter and drier than they are farther north. But heavy gene flow from other areas can prevent such locally adaptive responses from ever taking hold. Quantity of gene flow is not the only consideration. Rather than try to accumulate genes like lottery tickets—the more you own, the more likely you are to have a winner—another strategy might be to seek out variants of proven value.
Salmon populations that are supplemented by hatchery-raised fish, for example, might be good candidates. Initially, managers would release hatchery fish of different genetic stocks while maintaining populations of each stock in reserve. When the released fish come back to spawn, managers could see which stocks were most successful. There are many variations on this theme. Perhaps we could help plants respond to global warming by moving southern, more drought-adapted individuals into northern populations.
Perhaps we could bring back blight-decimated chestnut tree populations by cultivating and transplanting disease-resistant individuals. This is clearly the conservation frontier. Although many strategies for evolutionary intervention have some theoretical weight behind them, few have been tested by rigorous modeling, let alone actual application. One thing, however, seems clear. Proceeding down this path will require rethinking and, in some cases, letting go of cherished ideas and values—such as preserving the full range of genetic and phenotypic diversity that past evolution has produced.
Stockwell et al. But the view ahead suggests that this may be an overly confining template for the conservation enterprise. Now when I imagine life in , I see flora and fauna that have been through several centuries of selective pressures strong enough to drive mass extinction and disrupt ecological patterns on a global scale.
To varying degrees, those survivors will be different biological entities from the species we know today. For many, the differences may have much to do with the fact of their survival. Stockwell, C. Hendry, and M. Contemporary evolution meets conservation biology. Trends in Ecology and Evolution 18 2 In a similar way, Jacob said that the study of evolution could benefit from the analysis of the main units in molecular biology, such as the structural genes and the regulatory genes , and from the analysis of the changes in the relations between the units involved in the regulation of cell physiology.
In his essay, "Evolution and Tinkering," Jacob assimilated his knowledge of molecular biology into his philosophical ideas about the nature of science and scientific method. The essay has ten sections. Jacob begins with an outline of his conception of the scientific worldview and the relationship between the natural and social sciences. In the first two sections, Jacob states that science is a human product that consists of a series of cultural attempts to delimit the possible by framing explanatory systems and bestowing unity and coherence upon the world.
Like mythology, science attempts to explain the actual by delineating the possible, including the unknown or the invisible. Science, Jacob claims, can be differentiated from other cultural myths by its commitment to experimentation, and its ongoing process of criticism and revision.
As such, science aims to provide only partial and provisional answers to questions about the world. The history of science, according to Jacob, depicts a pattern in which scientific knowledge begins as isolated pieces of knowledge in particular scientific domains, and develops into a unified account of phenomena.
In the third section, "The Hierarchy of Object," Jacob addresses the challenges of studying objects, such as living organisms, human language and behaviour, and social and economic structures.
Jacob argues against what he calls methodological reductionism , stating that it would be absurd to try to explain something complex, like democracy, by appealing to the structure and properties of its elementary physical particles. Nonetheless—Jacob notes—the laws that govern elementary physical particles constrain every higher level object of study, including political structures. Lower levels of the hierarchy of objects limit the range of possibilities for objects in higher levels.
In the fourth section, "Constraints and History," Jacob states that most objects of scientific study are complex organizations or systems influenced by a combination of constraints and history. For instance, he argues that emergent properties of a system can be explained by appealing to the components of the system, but they cannot be deduced from them. In other words, one can not predict the emergent properties of complex systems, like cells' and organisms' properties, from the properties of their components.
The complex nature of the objects of study constrains predictions. Thus, such objects require examination at more than one level of analysis. Furthermore, Jacob argues that, because complex objects can result from evolutionary processes, they are also constrained by history. For example, scientists have shown that the structure of a cell relies on its molecular elements and composition.
However, Jacob notes, any evidence of these molecular elements in prebiotic time is not sufficient to explain the origin of life on earth. Historical conditions, including highly contingent events, have played a role in the origin of life.
In the next two sections, Jacob introduces and develops the metaphor of tinkering to bring into focus the historical character of evolutionary theory.
Jacob begins, in the fifth section, by describing the process of natural selection as an imposition of constraints on open systems, or organisms. Natural selection, according to Jacob, is both a negative and a positive force. It is negative in the sense that it works to eliminate less fit variants in a population, and it is positive in the sense that it works to integrate mutations that accumulate over time to produce adaptations.
Jacob states that natural selection 's creative force is evident in its ability to recombine old material into novelties; new structures, new organs, and even new species. In section six, "Evolution and Tinkering," Jacob dismisses a comparison between natural selection and engineering for three reasons. First, unlike natural selection , an engineer works according to a pre-conceived plan of the final product.
Second, an engineer actively chooses her materials and has access to the best tools designed for accomplishing the task at hand. Natural selection, in contrast, affects the structurally and functionally imperfect parts of the biotic world and reconfigures existing systems into novel ones. Third, if the engineer is successful, the final product achieves a level of perfection.
0コメント