Crossing the boundary between natural and human sciences

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How life maintains itself

The role of chance

In a period where the “Human Genome’ looks like containing the secret of life, it’s a good moment to remember that although genes do play an important role in every living organism, they are not the essence of life.DNA is a molecule and does not as such live. Life must be seen as a system, or as a process, in any case not as something static. At the moment the processes in a cell or a living being cease, life has ceased.

It is very difficult to give a definition of life, but it is not difficult to show that something is alive. Metabolism, growth, procreation and ability to react are the characteristics which we find in all living beings - and not in non-living matter – or at least not all of them at the same time.

Self regulation

One of the most fundamental properties of living beings – seldom mentioned in the list of characteristics of life – is homeostasis, the maintenance of its own structures and activities by a living system, in spite of various changes around it. A living being is a self-regulating system (also called ‘autopoietic', = ‘creating itself’). The descendants of a cell or living being not only get the DNA, but also the system, the organisation, of the cell or the organism.

Every unicellular being is capable of maintaining its own structure within changing external circumstances – in spite of the fact that it is an extremely small system.

Within multicellular beings the cells also possess ability; however these are specialised in certain functions. In its entirety the organism has a large degree of homeostasis. The best known and most apparent example is the temperature regulation of our bodies, but this is merely one of the many systems.

A body maintaining itself normally, being healthy, i.e. it maintains its homeostasis, regulates its processes, in spite of many influences, we find this so normal that we only think about it when something goes wrong with the homeostasis; when regulation appears no longer to operate normally. Indeed research into diseases has lead to the discovery of this regulation.

Thus AIDS has stimulated the research into immune processes and research into cancer has provided much information about growth and development – cancer is after all growth proceeding too fast.

Unpredictability

Unique to living systems – in contrast to physical processes – is a certain degree of unpredictability, of individuality.

Physical systems always operate in a regular fashion – at least this was so until recently. In modern ‘micro-physics' this appears not to be the case anymore (Quantum physics etc). The laws of physics always operate in normal circumstances, because we are concerned with large numbers of molecules and on average their reactions agree with the predictions of science. But if we look at ‘individual’ particles, chance appears to play a large role, and unpredictability occurs

This discovery was a confusing experience for physicists, which opened up new worlds. To biologists this is actually quite normal.

If we allow certain substances to react in a test tube, reaction follows expectations. So many molecules are present which collide and react with each other that the forecast reaction certainly follows.

Within a cell there may be only a few of every type of molecule present. As a rule the correct reaction occurs, but the chance that it will not occur is relatively big. Chance plays a much bigger role in the extremely small scale in which the processes occur. Here we speak of stochastic processes.

The role of chance in living processes is presumably larger than we imagine or like to imagine...

In modern biology we think that all functions of cells rest on ordered chemical processes within these cells, which attach to each other as parts of closely regulated systems within the cell. In multicellular creatures the activities are also subject to the organism as a whole. This means that the cell continually undergoes steering influences from outside while the cell itself sends signals to other cells determining their behaviour. The regulation of this system is based in the DNA.

We possess an estimated 35,000 genes of which a few thousands are ‘regulating genes’ of which a certain combination is necessary to ‘switch on’ a protein-coding gene.

Apart from this much is still quite unknown in this area. For example we do not know how behaviour can be determined by heredity – and to what extent that is the case.

The role of chance

Composition of membrane systems in a cell.

We have already seen seen that chemical reactions in the case of extremely small numbers of molecules do not necessarily proceed in a regular manner as they would in the test tube. The cell has ‘invented’ a system to prevent the molecules from roaming too much through the cell; the whole cell is divided into compartments by means of membranes, within which the processes occur (think of mitochondria and chloroplasts etc). Moreover many molecules adhere to the membrane, in a type of conveyor belt system.

But in spite of this factors involving chance play a fairly large role. Hallet and Halling, two British authors, in 1989 came to the conclusion that cells to a certain degree are subject to factors of chance. A certain measure of unpredictability of individual cell behaviour is the unavoidable consequence of the fact that the processes occur on an extremely small scale on the one hand and on the other hand the large number of reactions which take place in a cell.

This has far-reaching consequences: We can proceed from the idea that biological mechanisms completely and totally depend on physical and chemical regularities and as such could in principle be described in chemical and physical terms, but at the same time they are also subject to statistical laws, which means that at the very small scale at which they occur, chance plays a big role.

Illness and health

This insight is important for a better understanding of various aspects of life, namely matters such as illness and health.

In general the processes of life will run in a normal manner, because chance has no further part to play when we are concerned with millions of identical cells. If things proceed differently in one cell, this will have no effect on the organism as a whole. There are however certain situations where a chance error in a single cell has big consequences. This sort of situations occurs at the start of life when the organism only consists of one or a few cells, from which the whole organism will develop. If something goes wrong through chance effects, the complete development will usually cease sooner or later because vital functions are not in order, but sometimes a misformed child will be born. The most critical days are those preceding implantation (in the wall of the uterus). It is estimated that about 60% of fertilised eggs die before implantation, partly as a result of such errors of chance.

Also in the fully-grown organism these stochastic elements could be the basis for incalculable behaviour in cells; for example at the commencement of cancer the stochastic cause of deviation in the cell can be of crucial importance for the degree of virulence.

We must thus conclude that cancer does not always need an external cause. We know that radiation, smoking and the exposure to various substances can cause cancer, but it can also originate by itself.

The stochastic nature of biological processes implies that the course of the processes is never fully predictable.

In other words:

The occurrence of illnesses and deviations is inherent in life itself.

Life and suffering

Humans have always concerned themselves with the question of the meaning of suffering. Every religion and every philosophy tries to explain the meaning of human suffering.

Arnold van der Hooff (Dutch emeritus professor in microbiology) writes in ‘De schok der Biologie’ (= “The shock caused by (modern) biology”):

In my opinion no single philosophy and no single religion has been able to place the problem of suffering - which is inherent in human existence - into such a context that a reasonable person with some understanding of reality could be satisfied with it”.

John Stuart Mill wrote about his father:

"He found it impossible to believe that a world so full of suffering could be the work of a Creator who combined infinite power with perfect goodness and justice. His common sense spurned all sophistry used to throw sand in the eyes of humans and as a result of which they are blind to this undeniable contradiction"

Human suffering which seems to be inherent in our existence is usually ascribed to many factors. We think of natural disasters and epidemics. Christianity has always emphasised the innate wickedness of humans. But if it were ever possible to protect ourselves against natural disasters and to educate humans so well that they do not do any harm to others, even then suffering could not be banned. Suffering is a fundamental component of life.

The impressive magnificence of life has its downside. Life is by definition vulnerable. We can’t always point to a cause when something goes wrong. Nowadays people have the tendency to search for a cause in the operation of the genes, but deviations such as defective hearts, cleft palate, hydrocephaly, and Down’s syndrome can also arise due to completely coincidental minor errors during early development. It would be sensible to have this more widely emphasised, because parents often have the tendency to feel guilty over ‘faults’ in their child, or else onlookers try to blame the parents.

These factors play a role in embryonic development: not only deviations but also individual differences can be ascribed to stochastic processes: not only is everyone’s DNA unique, but also the location of connections in the brain for example are unique and in large part determined by chance.

What is life?

No one has ever been able to give a satisfactory answer to the question ‘What is life?’. We can describe life and as a rule have no problem to recognise something living, as such.

"No contrast is so enormous as that between what lives and what doesn’t live", says Joseph Wood Kruch – and in this (nearly) everyone will agree with him.

Until not so long ago – and for many people this is still the case – the difference was simple: living beings (certainly humans, often also animals) have a soul and inanimate things don’t. Whether animals and plants also have a soul – people could not or cannot agree about this question.

At death the soul left the body and lived on somewhere outside the observation field of relatives and according to some people returned sooner or later in a new body.

But through the development of the natural sciences this is for many people no longer credible; with the discovery that living matter is subject to all physical and chemical laws and that organic compounds can also be made in the laboratory. Until the start of the 19th century people thought that this could only be done by the ‘vis vitalis’ (= life force). Slowly the opposing idea became popular.

"The human body is a clock, a large clock interwoven with experience and competencies”, according to De Lamettrie in the 18th century. Even someone like Descartes thought this way.

Many people still think that a sort of life force exists which is responsible for the distinction (vitalism).

The not-vitalistic view amounts to the idea, that in matter as such something is present that provides the possibility for life. Especially since the development of the Quantum theory we have noticed that matter is less simply constituted than previously thought and that the characteristics cannot be exclusively be calculated by mathematics. According to these people a non-material principle that is necessary for life could also be found in non-living material and the contrast living/non-living could not be so great.

Emergence

A third way of thinking that also has much to do with homeostasis and is popular among many modern researchers and thinkers, proceeds from the idea that there is no separate life force, but that the specific structure and organisation of living cells and organisms cause the whole to be greater than the sum of the parts. In many cases this is clearly the case. This is a more or less ‘holistic’ approach according to which life could be an ‘emergence i.e. an unpredictable property which arises as a result of the order of structures.

Just as a nation is more than a collection of individuals, a collection of cells in a certain structure is more than the sum of cells: an organism which is capable of much more.

According to Arthur Peacock:

"The most important of the properties of matter is that it, if it is structured in certain manners, has all the properties that we call ‘life’.This also applies to human life."

According to Peacock and others the possibility of life should thus be built into the material from the start of the universe.

Holism

For this perspective the term ‘holism’ is used. Here it is advisable to distinguish this concept from the term as it is currently used outside the world of science (specifically by the followers of ‘New Age’).

To be able to research an organism in all its functions we must first research the parts, cells, organs, tissue etc. Each researcher knows that individual cells are not equal to cells in a living whole, but we can’t investigate the living whole as such.

We can’t really investigate a living system ‘holistically’. For practical reasons we have to proceed ‘reductionistically’ and in such a way attempt to understand the whole.

Circles outside science often look down on scientists because they proceed reductionistically ; the holistic image of the world would be the only true view.

The ‘kitsch of holism’ (Michel Korzec) sees these issues as biological knowledge combined with cosmology, Eastern and Western mysticism, ecology, cultural history and even quantum physics in one (tangled) whole. Alternative medicine also eagerly uses the term holism, because they say they treat the ‘whole person’.

Through this confusing use of language we should rather not use the term holism in biology, although the idea of the unity of body and soul, the unity of the organism is certainly important.

The essence of life is a subtle interplay of hereditary information, biochemical reactions and local structures” according to Prof. Dr R van Driel (biochemist at the University of Amsterdam).


The living cell

For three billion years life on earth consisted only of single-celled organisms. Afterwards multicelled organisms arose but even now the majority of living beings on earth consists of microscopically small beings about which we are not so well informed. But about the way in which single-celled beings and cells maintain themselves we are now discovering some things.

Until the sixties we learned at school that a cell consisted of “a small bunch of protoplasm with a nucleus”. The word ‘protoplasm’ has been dropped since then and we now know that the ‘cytoplasm’, the living content of a cell, is extremely structured. It consists of many clearly separated compartments in which processes occur. The compartments are separated by membranes and these membranes are more than just simple skin: many processes occur exactly on and in the membranes; the working elements often lie bedded in the membranes, so that complete conveyor-belt systems can be involved. Furthermore the membranes contain various small pumps bringing certain molecules from one to another section of the cell or pump these into or out of the cell.

Alongside this a cell contains a complete ‘skeleton’ composed of small tubes (microtubes) and bars or threads (microfilaments), that locate many processes, or secure them and if nessecary ensure movement of the whole cell.

A static image of the cell contents is just as wrong: diverse compartments fuse or separate, are transported through the cell, built anew or demolished. Dynamic and (seemingly) chaos control life within the cell.

With modern techniques such as fluorescent microscopes and dyes we can follow the movement of individual molecules in the cell and make three- dimensional images of the structures.

How is a gene switched on or off at a certain moment? This is one of the fundamental questions which for example also belongs to the problem of differences between species: the hereditary material of mice and men  differ only very slightly. It seems the fairly large differences between the two species can be explained by the difference in the moment in which some of the genes are switched on or off during embryonic development.

Parts of DNA that are not functional are packed tightly together and therefore can’t be reached and can’t be read. Certain genes (regulator genes) seem to play the role of ‘switch controller’. In all examined animals these are fairly identical, but why and how they switch on and off, is not yet known. The cell is a democratic system and not a ‘DNA-dictatorship.

Biologists and ordinary persons nowadays have the tendency to ascribe everything that occurs in the cell to DNA. The regulation of all processes is ascribed to a single factor (a gene or a protein). In reality it is much more complicated and we should see the cell as “a complex environment of interrelated processes”.

This description is due to Prof. Westerhoff (microbiologist and mathematical biochemist at Amsterdam). He invented the “Hierarchical Control Theory”, which describes the cell as a sort of democratic society where different proteins have ‘power’, that is they co-direct cell activities.

Co-operating yeasts

During research on yeast cells, that convert glucose to alcohol, Westerhoff and his co-workers discovered that the speed of the process oscillates and that its frequency is not dependent on one single factor, but a number of factors, which each has its ‘say’. Until recently it was thought  that the speed of a process always depended on the slowest working enzyme, the limiting factor. The regulating of the speed appears thus to be more complicated.

Yeast cells

Research of yeast cells brought to light that the cell activity is not constant but fluctuates. The strange thing was that all yeast cells in a colony appear to oscillate simultaneously.  They appear to communicate, which one would not expect in unicells. By taking samples from breeder liquids in extremely short intervals, researchers discovered that the concentration of acetaldehydes in the liquid between cells also oscillates. This substance is apparently shed and observed. In some or other way the cells can then synchronise their activities.

According to Westerhoff it is possible that this collective rhythmical yeasting also has a useful function: in nature the yeasts are found together with bacteria and moulds on overripe fruits, from which glucose gradually leaks. At the moment that all yeast cells exhibit the most activity, they absorb all the glucose of that moment.  Afterwards their activity is suspended momentarily (20 to 30 seconds), while the alcohol content rises (“while the yeastcells become drunk”). The competitors then have no food and cease their processes, until theamoment more glucose becomes available again, but just then the yeastcells are at their next top-activity and quickly drink up all the glucose. The other consumers in place are repeatedly wrong-footed by this (just as they could start up again, the glucose has been used up) and die.

In biochemical research examining such ecological aspects of events within the cell is not very conventional. That a cell is greater than the sum of separate biochemical processes, is another idea (also holistic in a certain sense), on which people such as Westerhoff are attacked by others.

The thought that a living whole is more than the parts, arouses suspicion in some researchers, because they suspect it belongs to New-Age imagery. Westerhoff denies this and calls the concept precisely anti-metaphysical: by searching for the connections, we can indicate exactly that there is nothing mysterious in the system.

With modern techniques we can follow the path of individual molecules in the cell and investigate the spatial division within the cell. With this it is possible to get an impression of the connectedness of different processes.

Louise E. Pihlajamaa-Glimmerveen

Read also the article “Antichaos and evolution” and the article “Chaos and fractals in human physiology”on this site.


Referenced literature

Karl Sigmund GAMES OF LIFE  Explorations in ecology evolution and behaviour (Penguin books 1995)

Evelyn Fox keller THE CENTURY OF THE GENE (Harvard University Press 2001)

 Steven Johnson EMERGENCE (Penguin 2001)

J.O. La Mettrie L’ HUMAN MACHINE (1748)

and several articles from Scientific American.

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by

drs. L.E. Pihlajamaa-
Glimmerveen

 


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