an essay in the series science perspectives
April 18, 2020 leave a comment
An infection comprises three aspects: the invasion of an organism, the host, by pathogens, the multiplication of these pathogens and the release of toxins in the process, and the host’s reaction to all that. Such infections occur very often during the lifetime of a host and mostly go unnoticed because of sophisticated protections. Some infections are so strong, however, that they noticeably interfere with the host’s normal function. They lead to a disease, which the host can cure in most cases, albeit often at significant costs. If this fails, the host permanently looses important functionality and may even die.
Pathogens originally emerge from mutations, which are imperfections in the replication process. If viable at all, these turn into competitors or predators. Different evolutionary strategies – balancing replication rate and complexity of organism – then lead to vastly different sizes of different lines, and to correspondingly different replication rates. One set of such lines, among several others, are hosts and pathogens.
Pathogens are an unavoidable consequence of evolution.
We often think of pathogens as viruses or bacteria, which emerged right with the origin of life some 4 billion years ago and continued to evolve jointly with the unfolding higher life ever since. However, as pathogens are an unavoidable consequence of evolution, they emerge at every level of evolution along the ever same mechanism: imperfect replication, competition-predation, and finally following different evolution strategies. Higher up on the evolutionary scale, such splits lead to pathogens that are very much larger than viruses and bacteria and are rather called parasites. This can be followed all the way up to the current evolutionary peak – humankind’s culture – parasitic concepts arising from incomplete understanding followed by simplification.
For a deeper conceptual understanding of the “infection-protection” complex, we apparently first need to consider the necessities and consequences of evolution.
The evolution of life is driven by two main stresses that result from the need of each organisms to (i) gain resources and (ii) protect itself from becoming a resource.
Resources are gained from the environment. They are required for building, maintaining, and operating the organisms’ structures. These in turn provide the functionality for it to gain and to protect.
Organisms at whatever evolutionary level are highly improbable structures and thus precious. At the very least, they constitute a resource. Indeed, part of the energy and building blocks required to build them can be gained by others as the organisms die or get killed. This is the predator-prey dynamics that operates through all levels of life, from bacteria and their phages all the way to the vegetarian or non-vegetarian human consumption. At a more advanced level, the structures of the exploited organism are not destroyed but at least in part redirected towards the goals of the exploiting organism, towards its gain of resources and protection. There indeed is a huge spectrum of such situations including endosymbiosis at the level of microorganisms, animal husbandry by humans, the microbiome of higher animals including humans, and viral diseases in plants and animals. These examples cover same-size exploitation as well as large exploiting small and vice versa, and they range from mutually beneficial to one-sided detrimental.
Evolution is fundamental and inevitable, and it is not restricted to biology.
These needs for gaining resources and for protection are fundamental to all evolving systems. They already existed for the first chemical reaction systems on the way towards life, long before biological life had actually started. And they continue to be commanding at the current highest level of evolution beyond the purely biological realm, that of humankind’s cultural evolution. Examples in case are knowledge and operational capabilities gained by individuals and groups. These again are subject to the same attack mechanisms of consumption and exploitation as found in biological systems, and they are eventually protected as intellectual property.
coevolution of life and its environment
As life unfolded, the corresponding systems for gaining resources and protection became ever more complicated with evolution’s mechanics leading to several hierarchical yet closely integrated layers. That unfolding did not occur in isolation, of course.
The evolution of life was strongly linked to the specific non-living environment. These include geochemistry, landforms and soils, water bodies, and the atmosphere. The various aspects of the non-living environment all follow their specific laws like chemical reaction kinetics or fluid dynamics. In addition, these aspects also got modified through the action of the diverse life forms. Such modifications range from composition, for instance the oxygen concentration in our environment, to structures and functionalities, for instance the landscapes in vegetated regions.
The other determinant of life’s unfolding is its own dynamics, the emergence, growth, competition, cooperation, migration, and eventual vanishing of the different species. Life indeed is a complex autocatalytic system, one that is self-organized and self-amplifying. On top it is evolving, creating ever new lines and levels.
Neither life nor the non-living environment can be understood without the respective other.
Apparently, form and function of any currently living organism can only be understood in the light of its coevolution with its non-living and living environment.
the red queen’s view
Evolution and coevolution are cozy words for actually quite grim situations. Indeed, our very being is based on the struggle for existence of previous species and beings, as popularized by Charles Darwin but indeed much older. It is often also referred to as an arms race, for resources and protection, or as the Red Queen’s view.
“Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!”Red Queen to Alice, in “Through the Looking-Glass, and What Alice Found There” by Lewis Carroll, 1871
And, of course, it is not just previous species and beings who struggled for existence, it is also us. It is manifest on all scales, from our daily competitive skirmishes to the battles of large tech companies over dominance, or that of nations and cultures, all the way to humankind’s big question: will we find a good way to survive on that planet with its limited resources?
There is an often cited way out of this struggle: cooperation. That is just an apparent solution, however, as it transfers the struggle from the individual to the cooperating group. Indeed, to the best of our knowledge, evolution is as fundamental a law as that of energy conservation and attempts to evade it are as futile as the perpetuum mobile was.
The struggle for existence with its two main stresses – gaining resources and protecting one’s existence – leads to a wide range of approaches that balance them in different ways. Two extreme strategies are: grow big and complicated or become small and simple.
grow big and complicated
Growing big and complicated eventually leads to highly sophisticated organisms with a complex hierarchy of strongly interacting levels, from the biomolecular machinery through the organs to the entire organisms. These provide a wide array of functions from the digestion of food through multilayered protection to exquisite cognitive and operational capabilities. The price for this is a high demand for diverse essential resources, correspondingly low population densities, and a low reproduction rate due to the high cost of building and maintaining complicated structures.
become small and simple
Becoming small and simple follows the contrasting approach to minimize the demand for resources, both in quantity and in diversity. This allows for vastly larger populations with correspondingly higher densities, and for much shorter reproduction times.
There are about 5’000 times more bacteria in a human body than humans on planet Earth and they can reproduce about 1’000’000 times faster than a human.
On the extreme end of life, there are bacteria, single-celled organisms that come with a complete biomolecular machinery, hence can live on their own. They are found everywhere in our environment in soils, in the ocean, hundreds of meters deep in the sediment, in slushy biofilms, but also in the kitchen sponge. When we think of them near us, we usually see them as threatening intruders. However, bacteria are not only in the environment, but they also occupy plants and animals, including humans. Indeed, of the complete cells within our body, some 90% are bacteria and only 10% belong to our organism proper. They are mostly in the gut, but also on our skin, and they typically are beneficial even essential for the operation of our body.
Viruses go yet a step further in minimizing. They no longer contain the biomolecular machinery for their reproduction but merely the information on how to do it. They thus need a host with such a machinery, inject their information, and correspondingly redirect the machinery’s operation.
Viruses obviously cannot exist on their own and need some living host, even if it is just bacteria. The same is true for many bacterial species that can only exist in a suitable host. In return, they often provide essential functions that range from the digestion of diverse foods to protection against pathogens. Naturally then, the two extreme strategies remain strongly coupled as they coevolve in an endless dance within a host’s body as well as in the exchange with its environment. That is the basis for beneficial symbiotic and detrimental pathogenic interactions across all scales of life.
The separation in size reflects just one pair of extreme evolutionary strategies and there is a whole continuum between them. Along the middle way, roughly same-sized organisms interact, again in different modes that range from cooperation to predation. While the specific forms of same-sized and different-sized interactions are necessarily different, they are still largely analogous, with the same driving stresses and the same consequences of pushing forward on the evolutionary path.
its not just biology
Since evolution is fundamental and inevitable, the different strategies are not restricted to biology. Indeed, at the current highest level of evolution, humankind’s culture, we readily recognize hosts and pathogens, cooperators and parasites, or prey and predators, both individually and in concert. Examples are easily found in various of its facets. It is illuminating to follow them a bit, in social structures, in the economy, in computer codes, in art, and all the way to the spiritual realm.
defense against infections – our immune system
Besides predation, pathogens in the form of viruses, bacteria, and fungi are a major part of the “attack-stress” on life. Predation and infection are structurally very similar as are their evolutionary consequences.
With life and its pathogens coevolving, all organisms have potent defenses against their pathogens, lest they are exterminated. These defenses are collectively referred to as the immune system. It takes over the defense once pathogens have overcome the physical barriers of an organism.
Humankind has the most advanced immune system. It comprises three intimately interlaced layers that emerged one after another along the evolutionary path:
- The innate immune system is the deepest layer and is present in all life forms. It is already active in newborns, comes with a limited number of receptors that recognize pathogens-associated molecular patterns, and is linked with the body’s physiology, causing for instance inflammations.
- The adaptive immune system is the next layer and it evolved only in vertebrates. It comes blank at birth, but with the capability to develop defenses against novel infections, to “learn” some of their characteristics, and to maintain a “memory” of the eventually successful defense. This allows a fast and effective defense against later similar infections, often to the point of immunity.
- The cultural immune system, a term that is not well-established yet, is the layer that emerges in social species, from ants to humans. Upon detection of an infectious disease by a few individuals, actions are taken by specialized groups, sometimes even by the entire population to counteract it. Compared to the innate and the adaptive systems, the mechanisms here are more diverse ranging from societal reorganization to sophisticated vaccinations.
individual immune systems
The innate and the adaptive immune systems are both intrinsic to individuals and act only for them. The operation of the two systems is similar in that receptors detect biomolecular patterns that are characteristic for attacked cells or for pathogens. That detection is rather unspecific for the innate immune system but becomes much more specific as the adaptive immune system gets activated, and ever more so if repeated infections by the same or similar pathogens occur.
Detection starts a cascade of actions that range from modifying physiological processes like blood flow, amplifying detectable signals to enhance the response, recruiting and attracting killer agents, and activating the adaptive immune system. The actual killing and removal of the pathogens is done by a diversity of specialized cells through complicated and self-regulated procedures with several layers of ever stronger interventions. Indeed, the entire cascade of actions deepens and widens the longer the infection persists.
Detection rests on the distinction between “self” and “non-self”, here at the biomolecular level. This apparently is a key component of every immune system. Failure to recognize some malign agent prevents the defense mechanisms to set in. On the other hand, failure to recognize cells that belong to the own body leads to attacks on them and may end in severe autoimmune diseases.
Incidentally, while recognition here is at the biomolecular level, it is structurally analogous to our visual recognition, indeed to that through sound, smell, or touch. It is inspiring to follow this analogy a bit. With respect to cultural systems, it extends even further, to the recognition of ideas and concepts.
cultural immune system
The cultural immune system is a diverse conglomerate both in terms of types of attacks it handles and the specifics of the defenses. The attacks can be grouped roughly into two kinds:
- towards individuals, specifically viral and bacterial infectious diseases, and
- towards society as a whole and its culture.
Attacks of the second kind include old challenges like emerging revolutionary ideas or invading foreign cultures. New ones arise with our technological developments, from dumb computer viruses to sophisticated, large-scale coordinated interferences with anything from buying decisions to political choices.
Our cultural immune system is in full and rapid development. It does not just employ a given “infrastructure” to learn, as our individual adaptive immune system does, but it coevolves with our culture, with its technological capabilities, and with its social constructs. Hence, the “infrastructure” per se evolves. At the same time it is closely integrated with the individual systems, both for the detection of an attack and for the actual defense, as will be illustrated in the following.
focus on operation of cultural immune system
To keep things simple, the focus will be on attacks of the first kind, towards individuals. Attacks of the second kind and defense mechanism are structurally quite similar albeit the specific aspects are very different. Incidentally, this similarity is a natural result of the underlying autonomous evolution that is about to create a next layer of individuality.
Analogous to the individual immune system, a defense by the cultural system again consists of two simultaneous and coordinated cascades of actions:
- Social restructuring like isolation of infected persons and increasing the physical distance between susceptible ones facilitates the rapid slow-down of the pathogen’s propagation within the population and it allows to focus resources. This is analogous to a body’s physiological modifications.
- Combating pathogens either directly or indirectly reduces the pathogen’s population and may eventually even eliminate it. Direct attacks on the pathogen are through antibiotics, indirect ones through priming and supporting the individuals’ adaptive immune systems. That system then does the actual work of finding, killing, and removing the pathogens.
Both cascades are started by the detection of an attack, typically when sufficiently many people fall ill or even die with consistent symptoms. For instance, the defense against COVID-19 set in after 7 unusual cases of pneumonia were reported within 3 days in one hospital in Wuhan, China.
From an abstract perspective, contagious diseases are contact processes. The pathogen is transmitted from an infected person to a susceptible person upon contact. With a certain probability, depending on the strength of the immune system, that person then also becomes infected and continues the transmission.
The contact required for transmission may need to be very intensive, as in the case of HIV, or it may be through carriers that can cross large distances, as for the sleeping sickness, or it may even be through short-range microscopic carriers like water droplet emitted while sneezing, as with the normal flu. The details of the contact are an important determinant for the spreading of the disease from an infected person to its neighborhood. Another and independent determinant for the spreading of the disease is the traveling behavior of infected persons, from walking to the neighbor’s house to jetting around the globe.
mechanics of contact processes
Contact processes are well understood even though the details are very complicated, as indicated above. There are two key factors that determine if an infection develops into a pandemic:
- The density of susceptible persons within the contact range determines if the disease can spread at all. If the density is higher than the so-called percolation threshold, the disease will spread throughout the entire domain purely by contact. It will not infect everyone, but only a certain fraction of the domain. That fraction depends on the structure of physical contacts between the susceptible persons and on the degree to which the percolation threshold is exceeded.
The density of susceptible persons depends on the total population density and on the immunity, which can be inherent, acquired through earlier infections, or due to vaccinations.
- The travel behavior of infected persons, distances traveled and frequencies, usually are the main factor for the speed of a disease’s spreading. Through traveling, pathogens get transported much faster than through pure contacts and, importantly, across barriers that would otherwise be insurmountable. As examples think of an infected person taking a train from one city to another, maybe through the Alps, or taking a plane across the Atlantic. Travel leads to the emergence of infection centers, apparently out of the blue.
These two factors determine if a pandemic develops and how fast it spreads. They say nothing about its severity like the number of casualties or the economic impact. These are determined by other factors and processes.
An apparent reaction to stop an infectious disease is to isolate infected persons. This works if all persons show clear symptoms before they become contagious. However, many diseases are such that a person turns contagious before symptoms arise, or there indeed may be no clear symptoms at all. The current prominent example for this is COVID-19.
Understanding the determinants for the unfolding of a pandemic leads to more effective immediate counter-measures, which are costly, however: (i) increase the physical distance beyond the contact range to prevent local spreading, (ii) stop traveling to prevent jumping of the pathogen to more distant places, and (iii) impose this on all who are susceptible. It is the last point that drives the cost of the measure to unseen heights, at least in cultures structured as our current ones. Because at the outset of a new disease it is unknown who is susceptible and who is not, the entire population has to be “locked down”. This, in the limits of our current culture, leads to a large-scale shut-down also of the economy, with all its dire consequences including, down the line, collateral losses of lives.
Ideally, such a lock-down only has to be imposed for the lifetime of the pathogen. This time can be rather short, for COVID-19 for instance a few weeks. In practice, however, that time span is much longer. One reason is that populations are sufficiently diverse and individualistic to make a complete lock-down next to impossible. A more fundamental reason is that humankind depends on a set of essential resources to survive, at least water and food. These in turn require at least electricity and systems for the production, transport, and removal of waste. With this, a significant work force has to remain active and in contact among each other as well as with a large fraction of the population.
after the shock
Opening up a society after the immediate shock reaction and restoring it to its previous state is only possible after the second cascade – combating the pathogens – caught track and starts to produce effective antimicrobials or vaccines. This may just take a few months, more typically a few years.
Restoring society to the state before the pandemic is impossible without effective means to combat the pathogens.
Without effective means for the combat, opening up society is a delicate balance between keeping the density of susceptible persons below the percolation threshold and maximizing economic production and personal freedom. That balance cannot lead back to the status quo ante. Obviously, since otherwise the pandemic would never have started in the first place.
We cannot squeeze pathogens between our fingers, we can only combat them by action on their scale. Hence, our action must be transferred, from the scale of our culture down to the scale of the pathogens, from our sciences, technologies, industries, economies, sociologies down to the biomolecular processes within individual persons.
The technology that allows us to combat pathogens acts as an extension of our individual immune systems. This extension is based on huge research institutions with their knowledge bases, on pharmaceutical industries, on operational health care systems, and eventually on the social fabric that enables coordinated campaigns. While that system apparently no longer operates at the biomolecular and cellular level, it still delivers its final products there.
The benefits of such a technological system are obvious: the defense against an infection need no longer be “learned” individually by each person but, once gained, the “knowledge” can be transferred directly and quickly to all. As always, there are costs, and here they come in two realms. First, there is the external economic cost of the entire operation, which is offset, though, by the population’s higher productivity as individuals are less likely to fall ill. Secondly, there is the potential cost that the individual adaptive immune systems may deteriorate as they are served ready made and uniform “knowledge”. This cost only materializes, however, if the cultural subsystem breaks down, either due to some sociocultural eruption or because our science looses the arms race against the microbial and viral worlds.
antimicrobials — direct combat
For a wide range of microbial life, of eukaryotes, bacteria, and fungi, drugs are available that can kill them. This is not the case for viruses as none of our current drugs can destroy them. However, for a range of viruses we have drugs that can inhibit their replication, hence turn them ineffective.
The advantage of such an arsenal of drugs is that it can be deployed very rapidly, ideally upon identification of the pathogen, in analogy to the individual innate immune system. Such drugs are difficult to find and develop, however. It takes years and significant resources to find one against any particular disease. Even worse, once such a drug is deployed successfully, the target pathogens are often found to evolve rapidly out of reach for the specific attack path. Such antimicrobial resistance, which is mainly driven by the overuse of cheap and convenient drugs, is about to turn into a major challenge for our society.
vaccination — indirect combat
The underlying idea is to bring a healthy body into contact with the infectious agent in a manner that the adaptive immune system can “learn” without the rest of the organism being overwhelmed. First reports of such efforts date back to 1550 in China, when pus from a smallpox pustule was transferred under the skin of a healthy person. Obviously, this so-called inoculation is very dangerous. Around 1800, the first real vaccination was done in England by inoculating a healthy boy with cowpox and recognizing that he was then immune against the more deadly smallpox.
Today, in contrast to those early explorations, we know the agents behind the diseases – bacteria and viruses – and understand their biomolecular machinery reasonably well. As a result, vaccinations became ever more sophisticated in optimizing “learning” at a minimal “cost” for the organism. Today, vaccines contain the infecting agents in dysfunctional form – recognizable for “learning” but no longer able to replicate – or even just some proteins or toxins related to the infecting agents that are able to “educate” the system.
the red queen, again
The three parts of our current immune system – the innate, adaptive, and cultural subsystems – are in a continuous arms race with the microbial and viral realms. This is also the case for all other forms of life with their possibly fewer subsystems.
At the base of this race is the rapid evolution of microorganisms and viruses, which we recall to replicate about 1’000’000 times faster than a human. They have a further strong advantage in their favor: so-called horizontal gene transfer, which is the direct exchange of genetic elements during the organisms’ lifetime. This is functionally analogous to humankind’s cultural immune subsystem in that some aspect “learned” by one organism, for instance survival in the presence of a particular antibiotic, can be directly transferred to another. Hence, the race is not against a huge number of infectious agents, each with quite moderate capabilities. It is against a population that explores a huge number of different paths in parallel, and rapidly shares successful ones.
the larger threat…
Recalling the key factors that allow infections to develop into pandemics – the density of susceptible persons within the contact range and the travel behavior of infected persons – reveals that pandemics are not accidents or transitory phenomena, not at the current state of humankind’s culture. They are inevitable consequences of (i) humankind’s growing population, (ii) its increasing concentration in large cities, and (iii) the increasing travels of persons and shipments of goods.
Pandemics are neither accidents nor transitory phenomena. They are an inevitable consequences of our current culture.
If pandemics are inevitable, what about their cause, infections with novel pathogens?
A fundamental aspect of life is that all the diverse forms, from single-celled bacteria to humans, are compatible at the biomolecular level. They all use the same code to store and transmit their information and the same machinery for rearranging matter according to that information. In a sense, they all can communicate with each other.
All forms of life can “talk” to each other.
Since biological pathogens operate at the level of the biomolecular machinery, they cannot only be transmitted within a species but, in principle, across all life forms. Now there are barriers that aim to prevent this and they are very effective. That is why humans are not affected by most of the viruses and bacteria in the animal world, and vice versa. However, occasionally there are mutations or recombinations with existing human diseases that allow pathogens to overcome the barriers and jump to the human realm. Such diseases are called zoonoses. Notorious examples are the 1918 Spanish flu, the 2009 swine flu, Ebola, HIV, and recently COVID-19. Most human diseases indeed originate in animals. Some subsequently evolved into purely human diseases, for instance HIV, and there is also back-infection of of the animal realm, as happened with the H1N1 virus after the 2009 swine flu.
As humankind’s population increases, even more so its consumption of natural resources and correspondingly its occupation of land, the contact between humans and the animal world is also expected to intensify. With this comes a higher exposure to the animals’ viral and bacterial reservoir and thus possibly a higher infection rate.
With the current state and structure of our culture, pandemics are no longer isolated and surprising catastrophes but will become recurrent albeit still catastrophic events.
…and ways forward
With pandemics in our current culture inevitable, there are two ways forward that will be balanced, either through conscious decisions or through evolutionary processes. One is to increase the density of immune persons, the other one is to increase the physical distance beyond the contact range.
density of immune persons
The immunity of a population can increase at the individual level through the adaptive immune system or at the societal level through vaccinations. Correspondingly, the arms race is at the level of the individual or of the culture, with success and failure determining the survival, selection, and evolution of the respective level.
Relying on the individuals’ adaptive immune system is often referred to as herd immunity. It is both the natural and the most robust solution, unfortunately also the one with the highest cost in terms of human lives. It lets the pathogen propagate through the population until a sufficient fraction has become infected and turned immune. Once the density of susceptible persons falls below the percolation threshold, the pandemic will stop, even though the disease will continue to exist locally. The control of this, through partial lock-down, aims at keeping the rate of severe symptoms so low that the health system can cope with it. Herd immunity comes with two sorts of costs: the lives taken by the disease to reach and maintain immunity and the time span over which lock-downs have to be imposed with their impacts on, among others, the economic and psychological state of the society.
Using current estimates of parameters for COVID-19 gives some idea on the magnitude. For Europe, with a population of some 750 millions, assuming a necessary immunity fraction of 60%, and a rather conservative death rate of 1%, an additional death toll of 4.5 million people over the time span of the transition is expected. Further assuming, still for Europe, that the health system can absorb some 100’000 new infections per day, which today it cannot, the control would have to remain in place for more than 10 years. Bleak prospects. And they assume that immunity does emerges eventually, that the pathogen does not mutate significantly, and that no other pandemic rolls in.
Vaccination, if and once it becomes available, is a game changer. It cuts the rate of additional deaths as well as the duration of lock-downs. It also demands a continuing evolution of a culture’s technological capabilities to keep pace with that of the pathogen’s realm.
societal and cultural restructuring
The cost imposed on our culture by recurring pandemics is of a magnitude that merely adjusting the density of immune persons after every outbreak is insufficient. This is true even if our cultural immune system would be able to cope with every new wave within one to two years. Hence, the fundamental cause must be addressed.
The fundamental culprit is the size of the human population, the current structure of its social fabric, and its interlacing with the rest of the animal realm.
Apparently, human societies will have to restructure and with them their cultures. One step is reduction of primary infections through disentangling the human realm and that of other animals by respecting their space of living. A more important and robust step is physical distancing beyond the contact range. This is not “social distancing” as it is often called. Indeed, the physical distancing must be done without compromising social contact and our social fabric, which is at the very heart of humanity.
Fortunately, our technology is at a point where many tools are already available, at least to some extents. This includes communication and cooperation networks, largely robotic production and distribution, but also filters and masks that reduce the contact range at least locally and temporally. What now needs to be done is to rethink many of our core activities and eventually restructure societies and cultures accordingly, and at large. How do we work, teach, and celebrate, for instance? What physical contact is necessary? What is a social contact, a handshake, a “like” on some platform, a wave in a video contact,…, or a handshake with a physical avatar? How is our socialization going to change along the way? All this will affect our very essence since humans are social, intellectual, and spiritual beings but, importantly, also physical ones. A touch is important.
Such restructuring will inevitably lead to new cultures, eventually perhaps even to an evolutionary transition. Which of the current societal organizations or technological streams will prosper and prevail eventually, if any, is not clear at all. What is clear, though, is that our culture will be different from what we have today and that this will be an important step in humankind’s evolution. This indeed is how evolution works, the red queen, also beyond the biological realm.
What is different now is that we, both subjects and objects of the evolutionary step, do understand and have the capability to design and to decide, to some extent.